Effects of diabetes mellitus on the contractile activity of carbachol and galanin in isolated gastric fundus strips of rats.
The role of the cholinergic and peptidergic pathways in the impairment of gastric motility associated with diabetic gastroparesis was assessed at the postsynaptic level using isolated fundus smooth muscle strips. Maximal contractile responses to carbachol and galanin were significantly decreased in fundus strips isolated from rats rendered diabetic by a single intraperitoneal injection of streptozotocin (STZ, 70 mg/kg) 1, 4 and 8 weeks before experiments. We also observed notable decrements in the slopes and Hill's coefficients without conspicuous changes in the EC50 of the respective galanin concentration-response curves measured in strips obtained from STZ animals after 4 and 8 weeks. L-NAME reversed the above-mentioned alterations in an L-arginine-sensitive manner in STZ rats after 4 weeks but not in STZ rats after 8 weeks. The blood plasma nitrite/nitrate levels in STZ animals after 4 and 8 weeks were increased by 44.6 and 61.9%, respectively. Ca2+-independent nitric oxide synthase activity in gastric fundus strips and stomach corpus mucosa from STZ rats after 4 weeks was markedly enhanced by 37.4 and 31.9%, respectively, suggesting an enhanced nitric oxide production. In vivo insulin treatment prevented diabetes-induced alterations in smooth muscle contractility. We conclude that the smooth muscle dysfunction evoked by experimental diabetes causing diminished contractions of fundus strips to carbachol and galanin is at least partly due to the increased nitric oxide synthesis.
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Kyoto, Japan. roman@mb-kyoto-phu.ac.jp
R
R
Korolkiewicz
P
P
Rekowski
A
A
Szyk
S
S
Kato
T
T
Yasuhiro
M
M
Kubomi
K
K
Tashima
K
K
Takeuchi
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019004:Galanin / Q000494:pharmacology*; D005748:Gastric Fundus / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D018721:Muscarinic Agonists; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D013311:Streptozocin; D019004:Galanin; D002217:Carbachol; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester