m-35 and Disease-Models--Animal

It has been reported that galanin and its receptors might be involved in the modulation and transmission of nociception in the central nervous system. Our previous research has also demonstrated that galanin induces antinociception in the nucleus accumbens (NAc) of intact rats. However, the interaction between galanin and its receptors in the NAc and the underlying mechanism of suppressing pain transmission remain unclear. The present study seeks to determine the antinociception induced by galanin receptor (GalR)-1 stimulation in the NAc of rats with neuropathic pain. The left sciatic nerve of rats was ligated to mimic a neuropathic pain model. Western blots showed that the expression of GalR1 was significantly upregulated in the NAc of rats with neuropathic pain. Intra-NAc injection of GalR1 agonist M617 induced a dose-dependent increase in hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulations in rats with neuropathic pain. Also, the effect of M617 was attenuated by M35, a GalR1/2 antagonist; at the same time, M35 reduced the galanin-induced antinociception, suggesting that GalR1 mediates antinociception induced by galanin in the NAc of rats with neuropathic pain. Furthermore, we found that M617-induced antinociception in rats with neuropathic pain was stronger than the antinociception in intact rats. We also found that injections of M617 and galanin each induced significant increases in HWL, but the galanin-induced antinociception was stronger than that of M617. All these results suggest that GalR1 plays an important role in antinociception and that other GalRs also are involved in pain modulation induced by galanin in the NAc of rats with neuropathic pain.

Topics: Analgesics; Analysis of Variance; Animals; Bradykinin; Disease Models, Animal; Functional Laterality; Galanin; Gene Expression Regulation; Male; Nucleus Accumbens; Pain Measurement; Peptide Fragments; Rats; Rats, Sprague-Dawley; Receptor, Galanin, Type 1; Sciatica

Galanin (Gal), a bioactive neuropeptide, is widely distributed throughout the central nervous system and has diverse modulatory effects. To understand the central effect of this training-stimulatory peptide on insulin sensitivity, its antagonist M35 was injected into the cerebral ventricle in type 2 diabetic rats. A treadmill running of the rats was used to stimulate circulating Gal secretion and central Gal mRNA expression. The results showed that M35 significantly decreased glucose infusion rates in euglycemic-hyperinsulinemic clamp tests as well as 2-deoxy-[(3) H]D-glucose uptake and peroxisome proliferator-activated receptor-α expression levels in skeletal muscles. M35 also attenuated glucose transporter 4 (GLUT4) concentration in plasma membranes and total cell membranes of myocytes, and the ratios of the GLUT4 contents in the former to the latter in M35 groups were lower than those of each diabetic control. These results imply that endogenous Gal, acting through its central receptor, may facilitate GLUT4 translocation from cytoplasm vesicles to cellular surface of myocytes to accelerate glucose uptake and to enhance insulin sensitivity in healthy and type 2 diabetic rats. Gal and its relative agents are potential targets for treatment of type 2 diabetes mellitus and its complications.

Topics: Animals; Bradykinin; Cell Membrane; Deoxyglucose; Diabetes Mellitus, Experimental; Disease Models, Animal; Exercise Test; Galanin; Glucose Transporter Type 4; Insulin Resistance; Locomotion; Male; Muscle Cells; Peptide Fragments; PPAR alpha; Rats; Rats, Wistar; Receptors, Galanin; RNA, Messenger; Streptozocin; Tritium

The aim of this study was to determine whether enhanced galanin (GAL) release induced by exercise would elevate insulin sensitivity and glucose transporter 4 (GLUT4) concentration in the plasma membranes of skeletal muscle in type 2 diabetic rats. We used M35, a GAL antagonist to antagonize the GAL function and swimming training for four weeks to increase GAL release of rats. The blood samples were analyzed for GAL and insulin concentration. The euglycemic-hyperinsulinemic clamp test was conducted for an index of glucose infusion rates. Additionally, skeletal muscle was collected and processed for GLUT4 mRNA level and GLUT4 concentration. The present findings showed that plasma GAL levels after swimming training in all three trained groups were higher compared with each sedentary control and each preswimming level. The insulin levels after swimming in both M35 treatment groups were elevated compared with each diabetic control and each pretraining level. Moreover, M35 treatment reduced glucose infusion rates compared with each diabetic control, but swimming enhanced the rates in all trained groups compared with each sedentary control. Furthermore, M35 treatment reduced GLUT4 concentration and GLUT4 mRNA levels compared with each diabetic control. The ratio of GLUT4 contents in plasma membranes to total cell membranes in both drug groups were lower compared with each diabetic control. These results suggest that endogenous GAL may enhance GLUT4 contents and promote GLUT4 transportation from intracellular membrane pools to plasma membranes. GAL is an important hormone to regulate insulin sensitivity in skeletal muscle from type 2 diabetic rats.

Topics: Analysis of Variance; Animals; Blood Glucose; Bradykinin; Cell Membrane; Diabetes Mellitus, Type 2; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Galanin; Gene Expression Regulation; Glucose Clamp Technique; Glucose Transporter Type 4; Insulin; Male; Muscle, Skeletal; Peptide Fragments; Physical Conditioning, Animal; Rats; Rats, Wistar; RNA, Messenger; Streptozocin; Swimming

We compared the galanin antagonists C7, M35, M40 and galantide, for their ability to ameliorate acute pancreatitis (AP).. Galanin antagonists were co-administered with 7 hourly cerulein injections used to induce AP. Plasma amylase and lipase activities were measured as indices of AP, and pancreata were harvested at 12 h for histological examination and estimation of myeloperoxidase (MPO) activity.. Treatment with galantide, M35 and C7 ameliorated the AP-induced plasma hyperenzymemia by 40-75%. Administration of M40 did not significantly alter plasma hyperenzymemia. Galantide, M35 and M40 significantly reduced the pancreatic MPO activity by 65-80%, whereas C7 increased MPO activity. Galantide and M35 but not C7 or M40 treatment significantly reduced the AP-induced necrosis score by 30-50% compared to the AP alone group. C7 alone increased plasma lipase activity and the pancreatic necrosis score compared with saline treatment alone, whereas the other antagonists were without effect.. Galantide and M35 ameliorated the severity of AP, but M40 and C7 had mixed effects. Complex galanin pathways may be involved in cerulein-induced AP. M35 and galantide are potential therapeutic peptides for the treatment of AP and further evaluation should be considered. and IAP.

Topics: Animals; Bradykinin; Ceruletide; Complement C7; Disease Models, Animal; Drug Therapy, Combination; Galanin; Male; Mice; Necrosis; Pancreas; Pancreatitis, Acute Necrotizing; Peptide Fragments; Peroxidase; Receptors, Galanin

The effect of intracerebroventricular infusion of galanin and/or the galanin antagonist M35 was studied in the forced swim test. Animals were pre-exposed to water for 15 min 24 h prior to test. Immobility and climbing were assessed during the second, 5 min exposure to water. Rats receiving a single infusion of galanin (3 nmol) displayed a significant increase of immobility. This effect was blocked by co-administration of M35 (1 nmol). M35 alone (1 nmol) produced a significant decrease of immobility. The results further support the hypothesis that galanin may play a role in mood disorders, and that galanin antagonists may represent new candidates for antidepressant treatment.

Topics: Analysis of Variance; Animals; Behavior, Animal; Bradykinin; Depression; Disease Models, Animal; Drug Combinations; Galanin; Immobility Response, Tonic; Injections, Intraventricular; Male; Peptide Fragments; Rats; Rats, Sprague-Dawley; Swimming

There is currently some debate over a possible role of galanin in pain processing. It was recently reported that the levels of galanin in dorsal root ganglia (DRGs) seem related to development of allodynia after unilateral sciatic nerve constriction injury. In our present study, we aimed at characterizing the effect of exogenous and endogenous galanin on pain behavior in allodynic and non-allodynic rats in which the levels of galanin in DRG neurons are low and high, respectively [28]. The results show that in allodynic rats, the mechanical threshold increases dose-dependently after intrathecal (i.t.) injection of galanin, while no significant changes were observed in groups treated with the putative galanin antagonist M35 or saline. In non-allodynic rats i.t. injection of M35 induced a significant mechanical allodynic state, which did not occur after injection of galanin, bradykinin, the bradykinin fragment(2-9) or saline. The results suggest that in the present experimental paradigm exogenous galanin has an anti-allodynic effect in the allodynic rats, and that endogenous galanin has a tonic inhibitory effect in the non-allodynic group.

Topics: Analysis of Variance; Animals; Bradykinin; Disease Models, Animal; Dose-Response Relationship, Drug; Galanin; Hyperalgesia; Injections, Spinal; Ligation; Male; Neuralgia; Pain Measurement; Pain Threshold; Peptide Fragments; Physical Stimulation; Rats; Rats, Sprague-Dawley; Sciatic Neuropathy