Gastric secretion but not nitric oxide is involved in pentagastrin-induced gastric relaxation in conscious dogs.
Gastrin delays gastric emptying of liquids probably by reducing gastric tone. The mechanism responsible for the relaxatory effect induced by pentagastrin was unknown. The aim of this study was to investigate the effects of pentagastrin and the underlying mechanisms responsible for these effects. Could nitric oxide (NO) be involved as a mediator. Gastric tone was monitored with a flaccid bag introduced into the stomach via a gastric cannula and connected to a barostat. A series of pressure-volume curves with a 30-min interval were constructed by increasing intragastric pressure to a maximum of 14 mmHg (2-mmHg steps). Pentagastrin (4 micrograms kg-1 s.c.) facilitated the volume increases induced by isobaric gastric distension. This effect could be completely blocked by pretreatment with cimetidine (10 mg kg-1 s.c.) or by omeprazole (10 mg kg-1 p.o.). The effect induced by pentagastrin could be mimicked by histamine (0.16 mg kg-1 s.c.) and to a lesser extent by insulin (0.2 IU kg-1 i.v.). Cimetidine and omeprazole had no intrinsic effect on gastric tone. With an opened cannula, allowing the gastric secretions to leave the stomach, no increased gastric relaxation could be observed either in the presence of pentagastrin or in the presence of histamine or insulin. Nitro-1-arginine (L-NNA, 5 mg kg-1 i.v.) reduced the volume increases induced by distension. Unexpectedly, even in the presence of L-NNA, pentagastrin remained effective. In conclusion, pentagastrin induces a gastric relaxation via a mechanism which involves gastric secretion but not nitric oxide.
Meulemans
A L
AL
Department of Gastrointestinal Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Wellens
A L
AL
Schuurkes
J A
JA
D000818:Animals; D004285:Dogs; D005260:Female; D005755:Gastrins / Q000378:metabolism / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D010418:Pentagastrin / Q000494:pharmacology*
D005755:Gastrins; D009569:Nitric Oxide; D010418:Pentagastrin