vasoactive-intestinal-peptide and Nerve-Degeneration

Nurr1 is critical for the development and maintenance of midbrain dopaminergic (DA) neurons in mouse. Loss of Nurr1 function early during development in mice leads to the absence of midbrain DA neurons. Reduction of Nurr1 function in adulthood leads to a slowly progressive loss of striatal DA and markers for DAergic neurons, supporting its selective roles in the maintenance of DAergic neuronal survival and function. To understand the molecular mechanisms of Nurr1 action, our group has identified VIP as a potential target gene of Nurr1. Nurr1 regulates VIP mRNA and protein levels, and transactivates the VIP promoter through Nurr1-responsive cis elements. Nurr1 loss of function leads to the decrease of VIP mRNA level in developing midbrain, suggesting that Nurr1 is involved in the in vivo regulation of VIP expression in midbrain. Our group has also cloned a novel protein interactor for Nurr1. We identified a family of gene products that interact and regulate the activity of Nurr1 by screening yeast two-hybrid library and termed the longest splicing form, NuIP. In vivo NuIP protein is largely colocalized with Nurr1 in adult midbrain dopaminergic neurons. NuIP interacts and positively regulates the activity of Nurr1 protein and could also possibly mediate cross talk between Nurr1 and GTPase mediated signaling pathways. Other recently identified potential target genes and interacting proteins of Nurr1 are also summarized and discussed in this review.

Topics: Animals; DNA-Binding Proteins; Dopaminergic Neurons; Gene Expression Regulation, Developmental; Humans; Mesencephalon; Nerve Degeneration; Neurogenesis; Nuclear Receptor Subfamily 4, Group A, Member 2; Parkinsonian Disorders; Signal Transduction; Vasoactive Intestinal Peptide

To describe morphological changes associated with degeneration and regeneration of large fibers in the skin using a model of chronic compression of the median nerve.. We studied cutaneous innervation in 30 patients with chronic compression of the median nerve at the wrist. Before surgery, we assessed the symptom severity and performed neurography, quantitative sensory testing, and analysis of nerve morphology and morphometry in skin biopsies from the third digit fingertip. Fifteen patients repeated all tests 12 months after the surgery. Thirty age- and sex-matched healthy subjects were included in the study.. Clinical and neurophysiological basal assessment showed a moderate involvement of the median nerve. Quantitative sensory testing showed abnormal findings. The density of intraepidermal nerve fibers and intrapapillary myelinated endings was reduced. Myelinated fibers showed caliber reduction and nodal elongation. Meissner corpuscles had normal density but were located deeper in the dermis and their capsule appeared partially empty. During follow-up, patients exhibited a positive clinical and neurophysiological outcome. Quantitative sensory testing improved. Intraepidermal nerve fibers and intrapapillary myelinated endings remained unchanged, but the caliber of intrapapillary myelinated endings was increased. The neural component of the Meissner corpuscle filled the capsule of the mechanoreceptors that remained deeper in the dermis. The position of vasoactive intestinal peptide-immunoreactive fibers was more superficial compared to the basal assessment and controls.. We recognized and quantified the pathological changes associated with nerve degeneration and regeneration in skin and proposed new parameters that may increase the diagnostic yield of skin biopsy in clinical practice. Ann Neurol 2020;87:456-465.

Topics: Case-Control Studies; Female; Fingers; Humans; Male; Median Nerve; Middle Aged; Myelin Sheath; Nerve Degeneration; Nerve Fibers; Nerve Regeneration; Skin; Time Factors; Vasoactive Intestinal Peptide

Vasoactive intestinal peptide (VIP) exerts neuroprotective effects under various neurotoxic conditions in vitro. In the present study, we investigated the effects of VIP on transient ischemic brain damage. Focal cerebral ischemia was induced using middle cerebral artery occlusion (MCAO) for 120 min in the adult rat brain. Either a single intracerebroventricular injection of VIP or saline was given at the beginning of reperfusion. Forty-eight hours after MCAO, the rats were sacrificed for evaluation of the infarct volume and histological analysis. ELISA was performed to assay levels of serum S100B before being sacrificed. We also evaluated the blood-brain barrier (BBB) permeability using Evans blue dye injection method. In contrast to the cases treated with vehicle, the infarct volume was significantly (P<0.05) reduced, and terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) staining and immunoreactivity for S100B were also significantly (P<0.05) decreased in the ischemic hemisphere with VIP treatment. In addition, the elevations of serum S100B were significantly (P<0.01) attenuated in VIP-treated rats compared with those of control rats. Treatment with VIP did not result in a significant reduction of Evans blue leakage, although it tended to be lower than that in the control rats. Our data suggest that treatment with VIP reduces brain damage in ischemic rats, and this effect may be associated with the attenuation of apoptosis and S100B expression.

Topics: Animals; Apoptosis; Brain Infarction; Brain Ischemia; Disease Models, Animal; Male; Nerve Degeneration; Nerve Growth Factors; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Vasoactive Intestinal Peptide

Alzheimer's disease (AD) is characterized by extracellular deposits of fibrillar beta-amyloid (Abeta) in the brain, increased microglial-mediated inflammatory reactions in senile plaques, selective neuronal death, and cognitive deficits. The use of agents that limit microglial activation and inflammation in AD has recently emerged as an attractive therapeutic strategy for this disease. The vasoactive intestinal peptide (VIP), a widely distributed neuropeptide, has shown neuroprotective effects in acute brain damage in vivo and potent anti-inflammatory actions in central nervous system. Here, we report that VIP inhibits Abeta-induced neurodegeneration by indirectly inhibiting the production of a wide panel of inflammatory and neurotoxic agents by activated microglia cells. The inhibitory effect of VIP is mediated by blocking signaling through the p38 MAPK, p42/p44 MAPK, and NFkB cascades, the three major transduction pathways involved in the transcription of inflammatory mediators and the production of free radicals by Abeta-activated microglia cells. Based on its neuroprotective action and its efficacy in inhibiting a broad range of inflammatory responses, VIP may provide a novel therapeutic approach to AD.

Topics: Amyloid beta-Peptides; Animals; Cells, Cultured; Coculture Techniques; Inflammation Mediators; Mice; Mice, Inbred BALB C; Microglia; Nerve Degeneration; Neurons; Neuroprotective Agents; Signal Transduction; Vasoactive Intestinal Peptide

The aim of this study was to investigate the ability of aminoguanidine (AG) to prevent diabetes-induced changes in nitric oxide synthase- (nNOS), vasoactive intestinal polypeptide- (VIP) and noradrenaline- (NA) containing nerves of the rat ileum using immunohistochemical and biochemical techniques. Diabetes was induced in adult male Wistar rats by a single intraperitoneal injection of streptozotocin (65 mg/kg). AG was administered in the drinking water to control (1.8 g/l) and diabetic (0.9 g/l) rats over a period of 8 weeks. Diabetes caused a significant increase in the thickness of nNOS-containing nerve fibres (p<0.001) in the circular muscle, in nNOS activity (p<0.05) and in the size distribution of nNOS-containing myenteric neurons (p<0.001). The thickness of VIP-containing nerve fibres was significantly greater (p<0.01) and there was a significant increase in varicosity size (p<0.01) and proportion of VIP-positive myenteric neurons (p<0.01) in diabetes. NA levels were significantly reduced (p<0.01) and the size of varicosities containing tyrosine hydroxylase (TH) was significantly increased (p<0.001) in diabetes. AG treatment completely or partially prevented the diabetes-induced increase in nNOS activity, in VIP-containing varicosity size, and in fibre width of both VIP- and nNOS-containing fibres in the circular muscle but had no effect on the diabetes-induced increase in nNOS-containing neuronal size or proportion of VIP-containing myenteric neurons. In contrast to VIP, AG treatment had no effect on the increase in TH-containing varicosity size in diabetes and also failed to prevent the decrease in NA levels induced by diabetes. These results indicate that AG treatment for neuropathy is not equally effective for all autonomic nerves supplying the ileum and that diabetes-induced changes in NA-containing nerves are particularly difficult to treat.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Enzyme Inhibitors; Guanidines; Ileum; Immunohistochemistry; Male; Myenteric Plexus; Nerve Degeneration; Neurons; Nitric Oxide Synthase Type I; Norepinephrine; Rats; Rats, Wistar; Vasoactive Intestinal Peptide

Because the understanding of postoperative changes in arterial graft innervation is limited, this study was performed to characterize neuronal degeneration and regeneration events immunohistochemically in femoral arterial grafts transplanted to carotid arteries in rats. Specimens taken 1 day, 3 days, 7 days, 1 month, 3 months, and 5 months after surgery were assessed for vasoactive intestinal peptide, neurofilaments, growth-associated protein 43, tyrosine hydroxylase, and nitric oxide synthase isoenzymes. During neuronal degeneration, vasoactive intestinal peptide disappeared within 1 day, transmitter-synthesizing enzymes (nitric oxide synthase and tyrosine hydroxylase) had vanished by day 7, and neurofilaments (cytoskeletal markers) had essentially disappeared after 1 week. In the regeneration phase, the most robust axonal growth, as visualized by growth-associated protein 43, was observed at 1 month, followed by a gradual increase in neurotransmitter markers at 1 and 3 months, whereas the neurofilaments increased gradually up to the end of the 5-month observation period. Reinnervation proceeded from the proximal carotid (host) trunk distally to the graft. Axonal re-growth occurred mainly in arterial adventitia. Innervation density, as visually assessed, was denser in the graft than in the host. These findings suggest that 1) the main sequence of degeneration and regeneration follows that reported in other models of neuronal degeneration; 2) reinnervation of the arterial grafts comes mainly from the host arteries; and 3) the innervation density in the graft may differ from that in the host, which may suggest target-derived regulation of innervation. The latter finding may have clinical implications. It suggests that for a good outcome it would be beneficial to choose a sparsely innervated graft rather than a densely innervated one.

Topics: Animals; Autonomic Nervous System; Carotid Arteries; Female; Femoral Artery; Follow-Up Studies; GAP-43 Protein; Immunohistochemistry; Isoenzymes; Nerve Degeneration; Nerve Regeneration; Neurofilament Proteins; Neurons; Nitric Oxide Synthase; Rats; Rats, Inbred Strains; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

Botulinum toxin is used to induce transient graded paresis by chemodenervation in the treatment of focal hyperkinetic movement disorders. While the molecular events occurring in motoneurons after mechanical nerve lesioning leading to muscle paresis are well known, they have been investigated to a lesser extent after chemodenervation. We therefore examined the expression of enkephalin (ENK), acidic fibroblast growth factor (aFGF), neurotensin (NT), galanin (GAL), substance P (SP), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY) in rat spinal motoneurons after chemodenervation of the gastrocnemius. In order to precisely localize the motoneurons targeting the injection site, retrograde tracing was performed in additional rats by using Fluorogold injections. ENK expression was upregulated in the region corresponding to the Fluorogold positive motoneurons, but also on the contralateral side and in more distant parts of the spinal cord. The highest upregulation occurred 7 to 14 days after injections and decreased over a period of three months. At 8 days, aFGF was slightly downregulated in all regions studied, single motoneurons showed NT expression, while expression of GAL, SP, VIP, and NPY could be detected neither in controls nor in toxin-treated animals. These alterations in gene expression were strikingly different from those described after axotomy. Our present findings give additional demonstration of the considerable plasticity of the adult spinal cord after botulinum toxin treatment.

Topics: Age Factors; Animals; Botulinum Toxins; Cell Count; Corpus Striatum; Enkephalins; Female; Fibroblast Growth Factor 1; Fluorescent Dyes; Galanin; Gene Expression; Motor Neurons; Muscle Denervation; Muscle, Skeletal; Nerve Degeneration; Neuropeptide Y; Neurotensin; Rats; Rats, Wistar; RNA, Messenger; Spinal Cord; Stilbamidines; Substance P; Vasoactive Intestinal Peptide

To evaluate the protective properties of peptides related functionally and/or structurally to vasoactive intestinal peptide (VIP), PC12 cultures were treated with iodoacetate as a model for neuronal ischemic/hypoxic injury. Brain tissue can be pre-conditioned against lethal ischemia by several mechanisms including sub-lethal ischemia, moderate hypoglycemia, heat shock, and growth factors. In the present study, a superactive VIP lipophilic analog (Stearyl-Norleucine17-VIP; SNV) was used to pre-condition media of PC12 cells. After removal of the conditioned media, the cultures were exposed to iodoaceate, which inhibits glycolysis. Protective efficacy against iodoacetate-induced injury was assessed by the measurements of lactate dehydrogenase (LDH) activity in the media. Treatment with iodoacetate for 2.5 h produced a twofold increase in LDH activity in the media. The protective effect of SNV had an EC50 of 1 pM. Comparison of the preconditioning time required for full protection by SNV showed no apparent difference between a 15 min and a 2 h incubation period prior to the addition of iodoacetate. Iodoacetate treatment produced a 20% decrease in the RNA transcripts encoding activity-dependent neuroprotective protein (ADNP), a novel glia-derived protein that is regulated by VIP. The iodoacetate-associated reduction in ADNP mRNA was prevented by pre-treatment with SNV. These effects imply that SNV provides a regulatory mechanism for ADNP synthesis during glycolytic stress. Furthermore, a short exposure to SNV provided potent protection from iodoacetate-induced toxicity suggesting that SNV may have therapeutic value in the treatment of ischemic/hypoxic injury.

Topics: Animals; Brain Ischemia; Disease Models, Animal; Enzyme Inhibitors; Homeodomain Proteins; Iodoacetates; Nerve Degeneration; Nerve Tissue Proteins; Neuroprotective Agents; Neurotoxins; PC12 Cells; Rats; RNA, Messenger; Vasoactive Intestinal Peptide

Different neuropeptide-containing nerve fibers (vasoactive intestinal polypeptide, substance P, neuropeptide Y) and nitric oxide synthase (NOS) positive nerve fibers were investigated to clarify their role in the function of human labial glands using immunohisto- and immunocytochemical techniques. The distribution pattern of all immunoreactive nerve fibers was similar both in the control and in the Sjögren's syndrome specimens. A large number of thin varicose vasoactive intestinal polypeptide and NOS positive nerve fibers were seen around or in close contact with the acini. Some of the immunoreactive nerve fibers were associated with the salivary ducts and blood vessels. Substance P and neuropeptide Y immunoreactive nerve fibers were located mainly around the blood vessels. Immunocytochemistry demonstrated that some of the positive nerve fibers were in direct contact with the acini, blood vessels and with the lymphocytes. The gap between the membranes of immunoreactive nerve terminals and the target cells was 40 to 200 nm. The number of the nerve terminals in Sjögren's syndrome specimens was decreased and some degenerated axons were also found. These results suggest that these neuropeptides and nitric oxide might act as a neurotransmitter in the regulation of secretion and blood flow in the labial glands. These fibers might also alter the neuroimmunological processes, because the investigated neuropeptides are known to be immunoregulators.

Topics: Axons; Blood Vessels; Humans; Immunohistochemistry; Lip; Lymphocytes; Nerve Degeneration; Nerve Endings; Nerve Fibers; Neuropeptide Y; Neuropeptides; Nitric Oxide; Nitric Oxide Synthase; Regional Blood Flow; Salivary Ducts; Salivary Glands, Minor; Sjogren's Syndrome; Substance P; Vasoactive Intestinal Peptide; Vasodilator Agents

These results provide morphological evidence for an alcohol-induced selective intrapancreatic nerve degeneration. This affected mainly the nerve fibers that are inhibitory of the exocrine pancreas, and might represent the morphological background of hypersecretory state of the pancreas in chronic alcoholism.. Intrapancreatic intrinsic nerves were studied by immunohistochemistry and electron microscopy after 4 mo of alcohol consumption and compared with control mice.. A dense network of nerve fibers was observed in the normal mouse pancreas around the blood vessels and ending on the exocrine cells. The presence of VIP, NPY, PP, SP, and serotonin in these nerves was demonstrated by immunohistochemistry. Four months of alcohol consumption did not result in apparent morphological changes of the pancreas. However, the majority of periacinar nerve terminals showed degenerative changes. Synaptic vesicles were diminished in number in some other nerve processes, whereas the perivascular nerve fibers were relatively well preserved. A slight decrease was found in the intensity of VIP and SP immunoreactivity, and the PP fibers almost disappeared.

Topics: Alcoholism; Animals; Ethanol; Immunohistochemistry; Male; Mice; Microscopy, Electron; Nerve Degeneration; Nerve Endings; Nerve Fibers; Pancreas; Pancreatic Polypeptide; Synaptic Vesicles; Vasoactive Intestinal Peptide

Syngeneic mouse islets were transplanted under the renal capsule of athymic nude (nu/nu) C57BL/6 mice. Likewise, neonatal rat islets or fetal porcine islet-like cell clusters (ICC) were transplanted into nude mice. The animals were killed at various times after implantation and the graft-bearing kidney was removed. The transplant was processed for microscopic examination with indirect immunofluorescence for neuropeptides and tyrosine hydroxylase, and with acetylcholine esterase staining to visualize nerve fibers in the graft. In all grafts, reinnervation with both afferent and efferent nerve fibers was encountered 20 weeks after transplantation. The pattern of reinnervation was quantitatively and qualitatively independent of the source of the implanted islets. These findings indicate that the pattern of reinnervation depends on the implantation organ and not on any inherent properties of the implanted endocrine cells. In addition, surviving vasoactive intestinal peptide-positive neurons within the fetal porcine ICC demonstrated an active ingrowth of nerve fibers into the ICC graft and the adjacent kidney parenchyma after transplantation. However, 12 or 16-24 months after transplantation, marked atrophy of all types of nerve fibers in the ICC grafts was observed. The reason for this late degeneration of nerve fibers is unknown, but it may be related to a failure to establish functional neural connections.

Topics: Animals; Animals, Newborn; Fetal Tissue Transplantation; Islets of Langerhans; Islets of Langerhans Transplantation; Male; Mice; Mice, Inbred C57BL; Mice, Nude; Nerve Degeneration; Nerve Fibers; Nerve Regeneration; Rats; Rats, Sprague-Dawley; Swine; Transplantation, Heterologous; Vasoactive Intestinal Peptide

Embryonic hypothalamic tissue originating from spontaneously hypertensive rats (SHR) was implanted in young normotensive Wistar Kyoto rats in an attempt to localize hypothalamic regions directly responsible for the induction of hypertension. A 25% increase in host systolic blood pressure as compared with the controls was recorded 3 months after implantation in the animals receiving rostral hypothalamic tissue (R-SHR), whereas blood pressure was not affected in the animals grafted with caudal hypothalamic tissue (C-SHR). The hypertension in the R-SHR group was accompanied by hypertrophy of the heart and kidneys. The number of vasopressin-immunopositive (VPi) parvocellular cells in the hypothalamic paraventricular nucleus (PVN) of the R-SHR group was massively reduced (by 72%), while that of the tyrosine hydroxylase-immunopositive cells displayed no change. In the suprachiasmatic nucleus of these animals the VPi cell number was unaltered. In the C-SHR, the amount of parvocellular VPi cells was also unaltered. Likewise, oxytocin-containing cells were the same in all groups. DNA nick-end labeling of the tissue revealed that PVN cells are undergoing programmed cell death. These results implicate a selective degeneration by hypothalamic PVN cells in the pathogenesis of hypertension.

Topics: Animals; Apoptosis; Brain Tissue Transplantation; Female; Fetal Tissue Transplantation; Hypertension; Hypertrophy; Hypothalamus; Immunoenzyme Techniques; Nerve Degeneration; Neurons; Pregnancy; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

The role of vasoactive intestinal peptide (V.I.P.) in nerve regeneration was investigated by assessing the changes in immunoreactive V.I.P. levels in rat sciatic nerves following injury and repair. 60 rats were divided into three surgical groups and one control group: In group I (primary repair), sciatic nerves were divided and immediately repaired; in group II (secondary repair), sciatic nerves were divided and repaired two weeks later; in group III (no repair), sciatic nerves were divided and not repaired; and in group IV (controls), sciatic nerves were exposed but not divided. Animals were sacrificed at three days and at weekly intervals. Their sciatic nerves were extracted and assayed for V.I.P. concentrations by a specific radioimmunoassay. The mean V.I.P. concentration varied between 22 and 46 pg./mg. protein in the control nerves and between 60 and 529 pg./mg. protein in all other groups. In the three surgical groups the levels were significantly higher in proximal than in distal stumps. Following nerve injury, there was an increase in V.I.P. concentration in the injured and repaired areas. This increase was greater in injured non-repaired areas and was highest in the first 48 hours, but continued during regeneration. The accumulation of V.I.P. in divided nerves occurred in response to nerve injury.

Topics: Animals; Nerve Degeneration; Nerve Regeneration; Rats; Sciatic Nerve; Time Factors; Vasoactive Intestinal Peptide

In 15 dogs, cobalt chloride solutions were infused close intra-arterially to perfuse a short segment of the jejunum. In an additional four dogs, the jejunum was perfused with the aqueous vehicle (perfusion control). All animals were killed after 1 mo and tissue samples from cobalt-treated and from nonperfused intestine (tissue comparison control) were obtained for electron microscopic and immunohistochemical studies. Segments infused with 0.25 g/dl cobalt solution showed minimal changes; the most striking feature was an increase of vasoactive intestinal polypeptide (VIP)- and substance P-containing neurosecretory granules. Cobalt chloride at higher concentrations (0.75-1.5 g/dl) induced degeneration of ganglion cells and axons in both the myenteric and submucosal plexi. In contrast, the smooth muscle and the mucosal cells of the cobalt-perfused intestine showed no histological abnormalities. Immunohistochemical staining of tissues treated with 0.75-1.5 g/dl cobalt solutions revealed absence of substance P, Met-enkephalin, and VIP immunoreactivity in all section studied; control segments showed the presence of all three peptides. Cobalt chloride in concentrations of 0.75-1.5 g/dl causes degeneration of intestinal intramural nerves and provides an experimental model suitable for studying the role of these nerves in small intestinal function.

Topics: Animals; Axons; Cobalt; Cytoplasmic Granules; Dogs; Jejunum; Lysosomes; Male; Microscopy, Electron; Myenteric Plexus; Nerve Degeneration; Nerve Fibers; Vacuoles; Vasoactive Intestinal Peptide

The output of amylase into saliva secreted after injection of methacholine or substance P was increased after parasympathetic denervation, but the salivary concentration of amylase was unchanged. The increased output corresponded to the increased flow. Isoprenaline injected during the methacholine-induced secretion raised the output, more being secreted from the denervated than from the contralateral gland. Vasoactive intestinal peptide, given while substance P caused salivation, also increased the amylase output, but equally from the two glands.

Topics: Amylases; Animals; Isoproterenol; Male; Mandibular Nerve; Methacholine Chloride; Methacholine Compounds; Nerve Degeneration; Parotid Gland; Rats; Rats, Inbred Strains; Receptors, Adrenergic; Receptors, Muscarinic; Saliva; Substance P; Vasoactive Intestinal Peptide

A 32-yr-old man with myotonic dystrophy had a left hemicolectomy performed because of a megacolon. The colonic mucosa, smooth muscle, and connective tissue appeared normal by hematoxylin and eosin and trichrome stains and transmission electron microscopy. In contrast, the myenteric plexus had markedly fewer neurons than normal on the hematoxylin and eosin stains. Silver staining of the plexus revealed degeneration and decreased numbers of argyrophilic neurons, which were smaller and had fewer processes and a more uneven staining quality than controls. Many axons were fragmented, and increased numbers of glial cell nuclei were present in the plexus. Degenerative changes in the neurons were present in a patchy distribution on transmission electron microscopy. Immunohistochemistry revealed a decrease of the substance P- and enkephalin-immunoreactive fibers in the muscularis externa. This suggests that colonic motor dysfunction associated with myotonic dystrophy may be caused by a visceral neuropathy that involves the substance P- and enkephalin-immunoreactive fibers of the smooth muscle.

Topics: Adult; Colon; Enkephalins; Histocytochemistry; Humans; Male; Megacolon; Myenteric Plexus; Myotonic Dystrophy; Nerve Degeneration; Nerve Fibers; Neuropeptide Y; Radiography; Substance P; Vasoactive Intestinal Peptide

Augmentation of the rat parotid salivary secretion to intravenous injections of substance P (SP) occurred when SP was combined with vasoactive intestinal peptide (VIP), or stimulation of the auriculo-temporal nerve in the presence of atropine and the adrenergic blockers, dihydroergotamine and propranolol. The largest increase was obtained when SP (0.5 micrograms kg-1) was used together with subthreshold doses of VIP (84% at 0.05 micrograms kg-1 and 105% at 0.5 micrograms kg-1) and low frequency stimulation (92% at 2 Hz and 97% at 5 Hz), which did not produce any salivary secretion by itself. There was no facilitated secretion when VIP and nerve stimulation were combined. Amylase output was much larger (250-500%) when SP was combined with nerve stimulation (0.5-5 Hz) or VIP (0.005-5 micrograms kg-1) than when SP was used alone. Similar results were obtained in rats where the auriculo-temporal nerve was stimulated during the early phase (24-90 h) of Wallerian degeneration, when the nerve-induced responses were seemingly completely blocked. Our results are consistent with the hypothesis that both VIP and SP contribute to the atropine-resistant parotid secretion, and that they have a complementary role in the rat parotid exocrine function.

Topics: Amylases; Animals; Atropine; Dose-Response Relationship, Drug; Electric Stimulation; Female; Nerve Degeneration; Parasympathetic Nervous System; Parotid Gland; Rats; Rats, Inbred Strains; Saliva; Substance P; Vasoactive Intestinal Peptide

Thermic lesions in the medial septum of adult rats result in dark degeneration of terminal boutons in the stratum moleculare and hilus of the area dentata. While most of the degenerating terminals are in synaptic contact with non-reactive cells, part of them end on dendrites of VIP-like immunoreactive neurons.

Topics: Animals; Cervical Vertebrae; Electrocoagulation; Hippocampus; Histocytochemistry; Immunoenzyme Techniques; Interneurons; Microscopy, Electron; Nerve Degeneration; Neural Pathways; Neurons, Afferent; Rats; Rats, Inbred Strains; Vasoactive Intestinal Peptide

Levels of vasoactive intestinal polypeptide (VIP)- and substance P (SP)-like immunoreactivity were measured in ocular and orbital tissues of albino rabbits. Substantial amounts of VIP were detected in the choroid (22.6 +/- 3.6 pmol g-1), and in the lacrimal (13.6 +/- 4.4 pmol g-1) and Harderian glands (20.2 +/- 4.9 pmol g-1). Somewhat less was found in the anterior uvea (3.6 +/- 1.1 pmol g-1), retina (5.4 +/- 1.3 pmol g-1) and optic nerve head (4.1 +/- 1.1 pmol g-1). Other tissues, including conjunctiva and extraocular muscle showed very little VIP-like immunoreactivity. Seven days after diathermic damage to the region of the pterygopalatine ganglion VIP was virtually eliminated from all these tissues. SP levels were also reduced, notably in the anterior uvea, probably due to concurrent destruction of sensory fibres. Electron microscopy revealed extensive degeneration of unmyelinated axons in the short ciliary nerves and in the choroid. No changes in ocular VIP levels were detected after sympathetic denervation, although a significant rise in SP was observed in the anterior uvea. The decrease in retinal VIP, believed to be confined to the amacrine cells, is considered to be a result of post-operative lid closure, rather than of VIIth nerve degeneration. Nevertheless, with this exception, VIP in ocular and orbital tissues of the rabbit appears to be contained exclusively within parasympathetic fibres of facial nerve origin.

Topics: Animals; Eye; Facial Nerve; Microscopy, Electron; Nerve Degeneration; Nerve Fibers; Orbit; Rabbits; Radioimmunoassay; Substance P; Sympathectomy; Vasoactive Intestinal Peptide