Effect of putative carcinoid mediators on gastric and small bowel transit in rats and the role of 5-HT receptors.
Whereas serotonin and substance P stimulate in-vivo and in-vitro myoelectric activity in the small intestine, their effects on transit are unclear. We used a validated in-vivo transit model in the chloral hydrate-anaesthetized rat to study the effects of serotonin, substance P and motilin, three putative mediators of carcinoid diarrhoea, on transit through the upper digestive tract. Intra-arterial serotonin accelerated gastric emptying of a radiolabelled liquid, while motilin accelerated overall upper gastrointestinal transit. Substance P slowed overall upper gastrointestinal transit without altering gastric emptying. The antagonists to serotonin receptor subtypes, R-zacopride (5-HT3) and ketanserin (5-HT2), also accelerated rat gastric emptying of liquids; in contrast, a 5-HT4 agonist, SC53116, resulted in a less pronounced effect on gastric emptying at the dose tested. We conclude that circulating substance P is unlikely to be an important accelerator of transit through the upper digestive tract; in contrast, hyperserotoninaemia significantly accelerates transit through the stomach, and 5-HT2 and 5-HT3 receptor subtypes may play a role in the motor effects of serotonin in the stomach.
Valdovinos
M A
MA
Gastroenterology Research Unit, Mayo Clinic, Rochester, MN 55905.
Thomforde
G M
GM
Camilleri
M
M
D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology*; D005746:Gastric Emptying / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects / Q000502:physiology; D008297:Male; D008954:Models, Biological; D009037:Motilin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*
D000930:Antidiarrheals; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D013373:Substance P; D009037:Motilin