neuropeptide-y and Hypertrophy

Peripheral neuropeptide Y (NPY) has been reported to regulate bone metabolism and homeostasis; however, its potential roles in growth plate chondrogenesis remain unclear. Here, we found that NPY expression decreased during chondrocyte differentiation in vitro and in vivo. NPY was required for chondrocyte proliferation; in contrast, knockdown of NPY facilitated chondrocyte hypertrophic differentiation. Administration of recombinant NPY in rat chondrocytes and metatarsal bones uncoupled normal proliferation and hypertrophic differentiation during chondrogenesis and thereby inhibited growth plate chondrogenesis and longitudinal bone growth. Remarkably, NPY activated the mTORC1 pathway in chondrocytes, whereas attenuation of mTORC1 activity by administration of rapamycin in vitro partially abrogated NPY-mediated effects on chondrocyte proliferation and hypertrophic differentiation. In addition, a combination of Y2R antagonist but not Y1R antagonist with NPY abolished NPY-mediated inhibition of metatarsal growth and growth plate chondrogenesis. Mechanistically, NPY activated Erk1/2 by NPY2R, then phosphorylated ERK1/2 activated mTORC1 to initiate PTHrP expression, which in turn promoted chondrocyte proliferation and inhibited chondrocyte hypertrophic differentiation. In conclusion, our data identified NPY as a crucial regulator of chondrogenesis and may provide a promising therapeutic strategy for skeletal diseases.

Topics: Animals; Cell Differentiation; Cell Proliferation; Chondrocytes; Chondrogenesis; Hypertrophy; Mechanistic Target of Rapamycin Complex 1; Neuropeptide Y; Rats

Reelin is a large secreted glycoprotein that regulates neuronal migration, lamination and establishment of dendritic architecture in the embryonic brain. Reelin expression switches postnatally from Cajal-Retzius cells to interneurons. However, reelin function in interneuron development is still poorly understood. Here, we have investigated the role of reelin in interneuron development in the postnatal neocortex. To preclude early cortical migration defects caused by reelin deficiency, we employed a conditional reelin knockout (RelncKO) mouse to induce postnatal reelin deficiency. Induced reelin deficiency caused dendritic hypertrophy in distal dendritic segments of neuropeptide Y-positive (NPY+) and calretinin-positive (Calr+) interneurons, and in proximal dendritic segments of parvalbumin-positive (Parv+) interneurons. Chronic recombinant Reelin treatment rescued dendritic hypertrophy in Relncko interneurons. Moreover, we provide evidence that RelncKO interneuron hypertrophy is due to presynaptic GABABR dysfunction. Thus, GABABRs in RelncKO interneurons were unable to block N-type (Cav2.2) Ca2+ channels that control neurotransmitter release. Consequently, the excessive Ca2+ influx through AMPA receptors, but not NMDA receptors, caused interneuron dendritic hypertrophy. These findings suggest that reelin acts as a 'stop-growth-signal' for postnatal interneuron maturation.

Topics: Animals; Calbindin 2; Calcium; Cell Adhesion Molecules, Neuronal; Dendrites; Extracellular Matrix Proteins; Hypertrophy; Interneurons; Mice; Mice, Knockout; Neocortex; Nerve Tissue Proteins; Neuropeptide Y; Parvalbumins; Receptors, GABA-B; Receptors, Glutamate; Reelin Protein; Serine Endopeptidases

The purpose of the present study was to clarify whether chronically elevated plasma neuropeptide Y (NPY) might affect heart function and cardiac remodeling in rats.. Male Wistar rats were administered NPY (85 μg for 30 days) by mini-osmotic pump subcutaneously implanted between the scapulae. Associated indices for heart function, cardiac remodeling and hypertrophy were evaluated.. Compared to the sham group, the baseline systolic blood pressure (SBP) in rats administered NPY was significantly increased; cardiac function was significantly decreased, as indicated by reduced ejection fraction (EF), left ventricular end-systolic pressure (LVESP), maximum change velocity of left ventricular pressure in the isovolumic contraction or relaxation period (± dp/dtmax) and increased left ventricular end-diastolic pressure (LVEDP); hematoxylin-eosin (H&E) staining detection displayed enlarged cell areas and a consistent increase in heart-to-body weight ratios (HW/BW) was observed; quantitative real time PCR (qRT-PCR) and Western blot analysis showed markedly increased expressions of β-myosin heavy chain (β-MHC), calcineurin (CaN) and phosphorylated p38 proteins, while no changes were found in the expressions of p38 total protein and the phosphorylations of JNK and ERK.. This study reported for the first time that long-term elevated plasma concentration of NPY could induce cardiac dysfunction and cardiac hypertrophy and this phenomenon could, in part, be mediated by the Ca2+/CaM-dependent CaN pathway and p38 mitogen-activated protein kinase (MAPK) signal pathway in rats.

Topics: Animals; Blood Pressure; Calcineurin; Heart; Heart Diseases; Hypertrophy; Infusions, Subcutaneous; Male; Neuropeptide Y; p38 Mitogen-Activated Protein Kinases; Rats; Rats, Wistar; Signal Transduction; Ventricular Function, Left; Ventricular Myosins; Ventricular Remodeling

We sought to identify mechanisms of beta cell failure in genetically obese mice. Little is known about the role of pancreatic innervation in the progression of beta cell failure. In this work we studied adrenergic innervation, in view of its potent inhibitory effect on insulin secretion. We analyzed genetically obese ob/ob and db/db mice at different ages (6- and 15-week-old), corresponding to different compensatory stages in the course of beta cell dysfunction. 15 week-old HFD mice were also studied.. All mice were characterized by measures of plasma glucose, insulin, and HOMA. After perfusion, pancreata were dissected and studied by light microscopy, electron microscopy, and morphometry. Insulin, Tyrosine Hydroxylase-positive fibers and cells and Neuropeptide Y-positive cells were scored by immunohistochemistry. Islets of obese mice showed increased noradrenergic fiber innervation, with significant increases of synaptoid structures contacting beta cells compared to controls. Noradrenergic innervation of the endocrine area in obese db/db mice tended to increase with age, as diabetes progressed. In ob/ob mice, we also detected an age-dependent trend toward increased noradrenergic innervation that, unlike in db/db mice, was unrelated to glucose levels. We also observed a progressive increase in Neuropeptide Y-immunoreactive elements localized to the islet core.. Our data show increased numbers of sympathetic nerve fibers with a potential to convey inhibitory signals on insulin secretion in pancreatic islets of genetically obese animals, regardless of their diabetic state. The findings suggest an alternative interpretation of the pathogenesis of beta cell failure, as well as novel strategies to reverse abnormalities in insulin secretion.

Topics: Adrenergic Neurons; Age Factors; Animals; Blood Glucose; Diet, High-Fat; Disease Models, Animal; Female; Hypertrophy; Insulin; Insulin-Secreting Cells; Islets of Langerhans; Mice; Neural Inhibition; Neuropeptide Y; Obesity; Tyrosine 3-Monooxygenase

The nucleus accumbens (NAc) contains high levels of neuropeptide Y (NPY), which is involved in the regulation of functions and behaviors that deteriorate with aging. We sought to determine if aging alters NPY expression in this nucleus and, in the affirmative, if those changes are attributable to the cholinergic innervation of the NAc. The total number and the somatic volume of NPY- and choline acetyltransferase-immunoreactive neurons, and the density of cholinergic varicosities were estimated in the NAc of adult (6 months old) and aged (24 months old) rats. In aged rats, the number of NPY neurons was reduced by 20% and their size was unaltered. The number of cholinergic neurons and the density of the cholinergic varicosities were unchanged, but their somas were hypertrophied. Nerve growth factor administration to aged rats further increased the volume of cholinergic neurons, augmented the density of the cholinergic varicosities, and reversed the age-related decrease in the number of NPY neurons. Our data show that the age-related changes in NPY levels in the NAc cannot be solely ascribed to the cholinergic innervation of the nucleus.

Topics: Aging; Animals; Cell Count; Choline O-Acetyltransferase; Cholinergic Neurons; Hypertrophy; Image Processing, Computer-Assisted; Male; Nerve Growth Factor; Neuropeptide Y; Nucleus Accumbens; Rats; Rats, Wistar

While the angiogenic effects of Neuropeptide Y (NPY) in myocardial ischemia and hypercholesterolemia have been studied, its effects on altering oxidative stress, fibrosis and cell death are not known. We hypothesized that local infiltration of NPY in a swine model of chronic myocardial ischemia and hypercholesterolemia will induce nerve growth and cell survival, while reducing oxidative stress and fibrosis. Yorkshire mini-swine (n=15) were fed a high cholesterol diet for 5 weeks. Three weeks after surgical induction of focal myocardial ischemia, an osmotic pump was implanted, which delivered NPY (n=8, high cholesterol treated, HCT) or the vehicle (n=7, high cholesterol control, HCC) for 5 weeks. Then myocardium was harvested for analysis. Assessment of myocardial function and perfusion was made the last intervention. Immunoblotting demonstrated significantly decreased levels of MMP-9 (p=0.001) and TGF-β (p=0.05) and significantly increased levels of Ang-1 (p=0.002), MnSOD (p=0.006) and NGF (p=0.01) in HCT. Immunohistochemistry results revealed significantly decreased TUNEL staining (p=0.005) and GLUT4 translocation (p=0.004) in HCT. The functional data showed significantly improved blood flow reserve (p=0.02) and improved diastolic function -dP/dt (p=0.009) in the treated animals. Local infiltration of NPY results in positive remodeling in ischemic myocardium in the setting of hypercholesterolemia. By initiating angio and neurogenesis, NPY infiltration improves blood flow reserve and restoration of fatty acid metabolism. The associated increased cell survival and decreased fibrosis result in improved myocardial diastolic function. NPY may have a potential therapeutic role in patients with hypercholesterolemia associated coronary artery disease.

Topics: Animals; Apoptosis; Cell Membrane; Cell Proliferation; Cell Survival; Chronic Disease; Coronary Angiography; Disease Models, Animal; Fatty Acids; Fibrosis; Gene Expression Regulation; Glucose Transporter Type 4; Heart Ventricles; Hypercholesterolemia; Hypertrophy; Male; Myocardial Ischemia; Myocytes, Cardiac; Neovascularization, Pathologic; Neuropeptide Y; Oxidative Stress; Swine

To investigate the role of Ca(2+)/calmodulin-dependent calcineurin (CaN) signaling pathway in neuropeptide Y (NPY)-induced cardiomyocyte hypertrophy in rat.. Cardiomyocytes of neonatal Wistar rats were cultured in the presence of 10 and 100 nmol/L NPY, and cyclosporine A (CsA) was applied to inhibit the activity of CaN. The protein synthesis rate, c-jun mRNA expression, CaN protein expression, CaN activity and intracellular Ca(2+) concentration in the cardiomyocytes were assessed.. Compared with the control group, (3)H-Leu incorporation and expression of c-jun mRNA in the cardiomyocytes treated with 100 nmol/L NPY increased significantly (P<0.05, P<0.001), and the effect of NPY was blocked by CsA. The activity of CaN (P<0.05), CaN expression (P<0.05), and Ca(2+) concentration in the cytoplasm (P<0.001) and nuclei (P<0.001) of the cells with 100 nmol/L NPY treatment also significantly increased compared with those in the control cells.. NPY can induce cardiomyocyte hypertrophy in rats, in which process Ca(2+)/calmodulin-dependent CaN signaling pathway plays an important role.

Topics: Animals; Animals, Newborn; Calcineurin; Cells, Cultured; Hypertrophy; Myocytes, Cardiac; Neuropeptide Y; Proto-Oncogene Proteins c-jun; Rats; Rats, Wistar; RNA, Messenger; Signal Transduction

Neuropeptide Y (NPY) has been shown to participate in cardiac hypertrophy. However, the mechanisms by which NPY induces cardiomyocyte hypertrophy are poorly understood. This study tested the hypothesis that NPY induces cardiomyocyte hypertrophy through Ca2+/CaM-dependent calcineurin (CaN) pathway in cultured neonatal rat cardiomyocytes. After 24-h treatment, NPY (100 nM) significantly increased 3H-leucine incorporation and c-Jun mRNA expression, concomitant with augment of CaN activity and protein level in cardiomyocytes compared to those cells without NPY treatment. The enhancement of 3H-leucine incorporation and c-Jun mRNA expression in cardiomyocytes treated with NPY were markedly inhibited by cyclosporine A (CsA), a selective inhibitor of CaN. We also investigated the effect of NPY on intracellular Ca2+ level in cardiomyocytes. There were no obvious changes in intracellular Ca2+ level of cytoplasm and nucleus in cardiomyocytes treated with NPY (100 nM) for 10 min. However, NPY significantly increased intracellular Ca2+ level of cytoplasm and nucleus in cardiomyocytes after 24-h treatment. The result suggested that NPY could induce hypertrophy of cardiomyocytes via Ca2+/CaM-dependent CaN signal pathway. The enhancement of [Ca2+]i caused by NPY may activate CaN signal pathways to mediate cardiac hypertrophy.

Topics: Animals; Calcineurin; Calcium; Cell Nucleus; Culture Media, Serum-Free; Cyclosporine; Cytoplasm; Hypertrophy; Leucine; Myocytes, Cardiac; Neurons; Neuropeptide Y; Proto-Oncogene Proteins c-jun; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Time Factors

Megencephaly, enlarged brain, is a major sign in several human neurological diseases. The mouse model for megencephaly (mceph/mceph) has an enlarged brain, presumably due to brain cell hypertrophy, and exhibits neurological and motor disturbances with seizure-like activity, as well as disturbances in the insulin-like growth factor system. Here, we report that expression of the neuropeptides cholecystokinin, enkephalin, galanin and neuropeptide Y is dramatically changed in mceph/mceph brains compared to wild type, as revealed by in situ hybridization and immunohistochemistry. The changes were confined to discrete brain regions and occurred in a parallel fashion for peptides and their transcripts. For cholecystokinin, mceph/mceph brains had region-specific up- and down-regulations in several layers of the hippocampal formation and increased levels in, especially ventral, cortical regions. Enkephalin messenger RNA expression was up-regulated in the dentate gyrus granular layer and in ventral cortices, but down-regulated in the CA1 pyramidal layer. Enkephalin-like immunoreactivity was elevated in mossy fibers of the hippocampus and the ventral cortices. Galanin expression was increased in several layers and interneurons of the hippocampal formation, as well as in ventral cortices. Galanin-like immunoreactivity was reduced in nerve terminals in the forebrain. Neuropeptide Y expression was increased in the hippocampal formation and ventral cortices. Whether the mainly increased peptide levels contribute to the excessive growth of the brain or represent a consequence of this growth and/or of the neurological and motor disturbances remains to be elucidated.

Topics: Animals; Brain; Brain Edema; Cholecystokinin; Enkephalins; Galanin; Hypertrophy; Mice; Mice, Inbred BALB C; Mice, Transgenic; Neuropeptide Y

Ras is a universal eukaryotic intracellular protein integrating extracellular signals from multiple receptor types. To investigate its role in the adult central nervous system, constitutively activated V12-Ha-Ras was expressed selectively in neurons of transgenic mice via a synapsin promoter. Ras-transgene protein expression increased postnatally, reaching a four- to fivefold elevation at day 40 and persisting at this level, thereafter. Neuronal Ras was constitutively active and a corresponding activating phosphorylation of mitogen-activated kinase was observed, but there were no changes in the activity of phosphoinositide 3-kinase, the phosphorylation of its target kinase Akt/PKB, or expression of the anti-apoptotic proteins Bcl-2 or Bcl-X(L). Neuronal Ras activation did not alter the total number of neurons, but induced cell soma hypertrophy, which resulted in a 14.5% increase of total brain volume. Choline acetyltransferase and tyrosine hydroxylase activities were increased, as well as neuropeptide Y expression. Degeneration of motorneurons was completely prevented after facial nerve lesion in Ras-transgenic mice. Furthermore, neurotoxin-induced degeneration of dopaminergic substantia nigra neurons and their striatal projections was greatly attenuated. Thus, the Ras signaling pathway mimics neurotrophic effects and triggers neuroprotective mechanisms in adult mice. Neuronal Ras activation might become a tool to stabilize donor neurons for neural transplantation and to protect neuronal populations in neurodegenerative diseases.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 1-Methyl-4-phenylpyridinium; Animals; Axotomy; Brain; Cell Count; Cell Size; Cells, Cultured; Choline O-Acetyltransferase; Enzyme Activation; Hypertrophy; Mice; Mice, Transgenic; Mitogen-Activated Protein Kinases; Motor Neurons; Mutation; Neurodegenerative Diseases; Neuropeptide Y; Neuroprotective Agents; Oxidopamine; Phosphatidylinositol 3-Kinases; Phosphorylation; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins p21(ras); RNA, Messenger; Signal Transduction; Substantia Nigra; Tyrosine 3-Monooxygenase

The neuropeptides and neuroendocrine cells are proven to exist in the human nasal mucosa. However, the pathophysiological and neuroimmunological roles of regulatory peptides in human nasal diseases require further investigation.. To investigate and compare the functional morphology and quantify the tissue concentration of regulatory peptides in the nasal mucosas of normal, allergic rhinitis (AR) and chronic hypertrophic rhinitis (CHR) subjects.. Human inferior turbinate mucosa specimens from 28 patients with AR, 25 patients with CHR and 15 patients without any nasal diseases were investigated. Using immunohistochemistry and radioimmunoassays, we detected the presence, distribution and concentrations of various neuropeptides (vasoactive intestinal peptides [VIP], neuropeptide Y [NPY], substance P [SP], calcitonin gene-related peptides [CGRP]) and general neuroendocrine markers (neurone-specific enolase, chromogranin A and somatostatin). Quantitative analysis of the stained fibres and cells were performed using a graphic AutoCAD program.. The presence and distribution of NPY, CGRP, and SP nerve fibres and neuroendocrine cells were similar among the three subject groups. AR subjects had significantly higher VIP and SP tissue concentrations. VIP fibres had highest density in AR subjects and these fibers predominantly innervated vessels. In CHR, VIP fibres primarily innervated glands.. VIP and SP may play an important neuroimmunological role in the pathogenesis of AR. VIP may lead to the hypertrophic changes of submucosal glands in the pathogenesis of CHR.

Topics: Calcitonin Gene-Related Peptide; Humans; Hypertrophy; Nasal Mucosa; Nerve Fibers; Neuropeptide Y; Neuropeptides; Neurosecretory Systems; Radioimmunoassay; Rhinitis; Rhinitis, Allergic, Perennial; Substance P; Turbinates; Vasoactive Intestinal Peptide

This study aims to investigate the roles of neuropeptides in the pathophysiology of human nasal diseases. By using immunohistochemistry and radioimmunoassay, we detected the presence, distribution and concentrations of the following neuropeptides in human nasal tissue: vasoactive intestinal peptides (VIP), neuropeptide Y (NPY), substance P (SP), and calcitonin gene-related peptides (CGRP). This was performed in human nasal inferior turbinate mucosa from 20 patients with allergic rhinitis, twenty-five patients with chronic hypertrophic rhinitis and 10 patients without any nasal disease conditions. The presence and distribution of NPY. CGRP and SP fibers among the three subject groups displayed no evident differences. VIP fibers were densely stained around the vessels in the allergic group. In contrast, these fibers were more prominently distributed around the submucosal glands of the chronic hypertrophic rhinitis group. The concentration of VIP and SP in human nasal inferior turbinate showed a significant increase in allergic subjects. Thus, VIP may be revelant to the hypertrophic changes of the nasal mucosa. Both SP and VIP may play significant neuroimmunological roles in the pathogenesis of allergic rhinitis.

Topics: Calcitonin Gene-Related Peptide; Humans; Hypertrophy; Nasal Mucosa; Neuropeptide Y; Nose Diseases; Respiratory Hypersensitivity; Rhinitis; Substance P; Vasoactive Intestinal Peptide

The neuropeptides which have been immunolocalised within the adrenal cortex have a role in regulating steroidogenesis and adrenal blood flow, but little is known of the mechanisms which regulate adrenal neuropeptide content. The present studies were designed to investigate the regulation in the rat of three adrenal neuropeptides, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and substance P (SP), looking at the effects of splanchnic nerve section and also investigating the effects of unilateral adrenalectomy on the neuropeptide content of the contralateral adrenal following 9 days of compensatory growth. Splanchnic nerve section, followed by a 10-day recovery period, caused a significant increase in immunoreactive NPY (irNPY) and irSP content, but had no effect on irVIP in the capsular/zona glomerulosa portion of the rat adrenal gland. In the inner zone/medullary fraction, however, irVIP was significantly decreased, while irNPY and irSP were unaffected by splanchnic nerve section. Unilateral adrenalectomy had no effect on the contralateral adrenal content of any of the peptides, although the left adrenal gland increased in size by around 60% 9 days after removal of the right adrenal. These data suggest that NPY and SP in the rat adrenal capsule/zona glomerulosa and VIP in the inner zones/medulla, are regulated, directly or indirectly, by splanchnic nerve activity, but that VIP in the outer cortex, and NPY and SP in the inner zones are regulated by another mechanism, which is, at present, unclear. These data do not support a role for VIP, NPY or substance P in the adrenal hypertrophic response to unilateral adrenalectomy in the rat.

Topics: Adrenal Glands; Animals; Female; Hypertrophy; Immunoassay; Neuropeptide Y; Rats; Rats, Wistar; Splanchnic Nerves; Substance P; Vasoactive Intestinal Peptide

Considerable evidence indicates an enhanced sympathetic innervation of resistance arterial smooth muscle in the spontaneously hypertensive rat (SHR) compared with its normotensive Wistar-Kyoto (WKY) control. In addition to sympathetic hyperinnervation, an increased vascular innervation by neuropeptide Y-containing fibers, which are known to exert a vasoconstrictive and trophic action in vascular smooth muscle, has also been described. In addition to genetic hypertension, the SHR expresses hyperactive behavior and hyperreactivity to stress. To determine whether the enhanced neuropeptide Y-immunoreactive vascular innervation is specifically associated with hypertension and/or these behavioral abnormalities, four genetically related, inbred rat strains were used: SHR, which are hypertensive and hyperactive; WKY rats, which are neither hypertensive nor hyperactive; WKHA, which are hyperactive but normotensive; and WKHT, which are hypertensive but not hyperactive. The present study demonstrated that whereas the hypertensive strains (SHR and WKHT) exhibited smooth muscle hypertrophy in both superior mesenteric and caudal arteries in adulthood (10 months) but not at a prehypertensive age (1 month), both arteries exhibited significantly increased neuropeptide Y-immunoreactive innervation at both ages. It was further observed that the mesenteric artery in WKHA, a normotensive strain, had significant smooth muscle hypertrophy at 10 months; however, neuropeptide Y innervation in this artery was no different from that of WKY controls. The findings indicate that there is a cosegregation of neuropeptide Y hyperinnervation of the vasculature with the hypertensive phenotype, evident as early as 1 month of life in the hypertensive strains, and this should be considered further as a contributory factor in genetic hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arteries; Behavior, Animal; Hypertension; Hypertrophy; Male; Muscle, Smooth, Vascular; Nerve Fibers; Neuropeptide Y; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Species Specificity

A prolonged infusion with neuropeptide-Y (NPY) caused a notable hypertrophy of the adrenal zona glomerulosa and its parenchymal cells in rats whose hypothalamo-hypophyseal axis and renin-angiotensin system were pharmacologically interrupted. Zona glomerulosa hypertrophy was associated with a significant rise in both basal and stimulated plasma levels of aldosterone. Zona fasciculata cells and the blood concentration of corticosterone were not affected. These findings suggest that NPY is specifically involved in the stimulation of the growth and steroidogenic capacity of rat adrenal zona glomerulosa.

Topics: Adrenal Cortex; Adrenal Cortex Hormones; Aldosterone; Angiotensin II; Animals; Corticosterone; Hypertrophy; Male; Neuropeptide Y; Rats; Rats, Inbred Strains; Reference Values

The distributions of nerve cells and fibers with immunoreactivity for the peptides enkephalin, gastrin-releasing peptide, neuropeptide Y, somatostatin, substance P, and vasoactive intestinal peptide were examined in specimens of myenteric plexus and external muscle from the pylorus of 20 infants with hypertrophic pyloric stenosis. These were compared with peptide distributions in pyloric samples from unaffected infants and adults. In the normal pylorus the circular muscle was richly supplied with fibers reactive for enkephalin, neuropeptide Y, substance P, and vasoactive intestinal peptide. In pyloric stenosis, these immunoreactive fiber bundles were either missing or less than 5% of normal. In contrast, there were reactive cell bodies and nerve fibers in the myenteric plexuses of both normal and affected specimens. In the samples from cases of stenosis, swollen nerve fibers that appeared to be in the process of degeneration were frequently encountered. It is concluded that infantile hypertrophic pyloric stenosis is associated with a loss of peptide immunoreactivity in nerve fibers in the circular muscle, although the same peptides are still revealed in fibers and in nerve cell bodies in the myenteric plexus.

Topics: Enkephalin, Leucine; Female; Gastrin-Releasing Peptide; Humans; Hypertrophy; Infant; Male; Myenteric Plexus; Nerve Fibers; Neuropeptide Y; Peptides; Pyloric Stenosis; Pylorus; Somatostatin; Substance P; Vasoactive Intestinal Peptide