Secretin at physiological doses inhibits gastric motility via a vagal afferent pathway.
Secretin is an important modulator of gastric motility. In this study, we investigated the site(s) and mechanism(s) of action of secretin to inhibit gastric motility, using an in vivo rat model. Intragastric pressure response to graded doses of secretin was recorded in anesthetized rats by a balloon attached to a catheter passed through an incision in the duodenum into the body of the stomach. The intragastric pressure was set at 10 cmH2O with balloon distension. Intravenous infusion of secretin (1.4, 2.8, 5.6, 11.2, and 22.4 pmol.kg-1.h-1) decreased intragastric pressure in a dose-dependent manner. The threshold dose was 2.8 pmol.kg-1.h-1, and the effective dose at 50% (ED50) was 5.6 pmol.kg-1.h-1, which produced physiological levels of plasma secretin. Pretreatment with hexamethonium (10 mg/kg) markedly reduced gastric motor response to secretin (5.6 pmol.kg-1.h-1). Bilateral truncal vagotomy also significantly diminished gastric motor responses to secretin. In contrast, secretin (5.6 pmol.kg-1.h-1) had no effect on gastric contraction evoked by electrical vagal stimulation (1.25-5 Hz) or carbachol (10(-6) to 3 x 10(-5) M). These observations indicate that physiological concentrations of secretin act via stimulation of presynaptic cholinergic neurons in a vagally mediated pathway. In subsequent studies, we demonstrated that perivagal treatment 4 days before with the sensory neurotoxin, capsaicin, abolished gastric motor response to secretin but did not affect contraction evoked by electrical vagal stimulation. Similarly, we also showed that gastroduodenal application of capsaicin for 30 min also markedly reduced gastric response to secretin. These observations indicate that physiological doses of secretin act on vagal afferent pathways originating from the gastroduodenal mucosa to induce gastric relaxation.
Lu
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Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109, USA.
Owyang
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D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004525:Efferent Pathways / Q000502:physiology; D004558:Electric Stimulation; D005769:Gastrointestinal Motility / Q000187:drug effects*; D018738:Hexamethonium / Q000494:pharmacology; D007262:Infusions, Intravenous; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology; D008297:Male; D008954:Models, Biological; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012633:Secretin / Q000008:administration & dosage / Q000494:pharmacology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D012633:Secretin; D018738:Hexamethonium; D002217:Carbachol; D002211:Capsaicin