Pharmacological regulation of postprandial gastrointestinal motility by glucagon in conscious dogs.
The physiological or pharmacological role of glucagon in the postprandial regulation of gastrointestinal motility has not yet been clarified. To clarify it, the following experiments were performed on conscious dogs. Antral, duodenal, jejunal and ileal contractile activities were monitored by chronically implanted strain gauge force transducers without restraint. The serum gastrin concentration in response to ingestion was measured by radioimmunoassay. 1) When glucagon (5 approximately 50 microg/kg, drip infusion for 5 minutes) was administered before ingestion of meal or 2 hours after ingestion, it inhibited postprandial motility dose-dependently in the antrum, while enhancing it in the duodenum, jejunum and ileum. 2) At the same time, glucagon inhibited the meal induced elevation of the serum gastrin concentration. 3) On the other hand, glucagon did not inhibit the contractions induced by pentagastrin (4 microg/kg,s.c.) or those induced by acetylcholine chloride (0.5 mg/kg, drip infusion for 10 minutes) in any region. 4) These glucagon-induced inhibitory effects in postprandial antral motility were not affected by phentolamine (0.5 mg/kg, i.v.) or nitro-L-arginine-methyl ester (L-NAME) (3 mg/kg/hr, drip infusion for 30 minutes). These results suggest that: 1) Glucagon inhibits the postprandial elevation of the serum gastrin concentration and thus inhibits postprandial antral motility. 2) On the other hand, in the intestine, glucagon-induced inhibitory responses might be reversed by glucagon-induced excitatory responses through preganglionic cholinergic motor neurons. 3) The mechanism of inhibition of gastrin release was not definite in my experiments, but one of the candidates may be activation of somatostatin release from the D cells by glucagon.
Shimatani
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First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
D000818:Animals; D004285:Dogs; D005260:Female; D005755:Gastrins / Q000097:blood; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005934:Glucagon / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010418:Pentagastrin / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D019518:Postprandial Period / Q000502:physiology*; D013004:Somatostatin / Q000378:metabolism
D005755:Gastrins; D013004:Somatostatin; D005934:Glucagon; D010418:Pentagastrin; D019331:NG-Nitroarginine Methyl Ester; D010646:Phentolamine