Search

Pentagastrin (PG) is a potent agent causing release of serotonin (5-HT) from patients with carcinoid tumors. The physiological release of 5-HT from gut enterochromaffin cells is controlled by beta-adrenoceptors. Studies on carcinoid tumor cell suspensions, acute or in culture, have shown that catecholamines (CA), but not PG, release 5-HT, thus indicating an indirect mode of action by the peptide. In this study the mechanism for release of 5-HT from the gut induced by PG was investigated in animal models. The test protocol for patients was used in anesthetized cats. Portal blood samples were drawn after PG injection (0.6 microgram/kg iv), which resulted in significantly increased levels of 5-HT at 3 and 5 min postinjection. The PG-induced release was totally inhibited after blockade of beta-adrenoceptors (propranolol) or of slow calcium channels (verapamil) as well as after adrenalectomy. Blockade of beta-adrenoceptors or slow calcium channels decreased the basal levels of 5-HT, while adrenalectomy caused no change. In separate experiments CA were measured after PG injection in caval blood, drawn at the level of the adrenal veins. There was a significant increase in the levels of dopamine and epinephrine postinjection, while the levels of norepinephrine were stable. The changes of CA levels after PG injection could be prevented by adrenalectomy. These results further suggest an indirect action of PG in the release of 5-HT from the feline gut via activation of beta-adrenoceptors by epinephrine released from the adrenals.

Substance P-like immunoreactivity (SPLI) was found in the luminal contents of the feline small intestine. A physiological role for endoluminal substance P (SP) was explored in in vivo experiments, where feline jejunal segments were endoluminally perfused with saline or a low concentration of SP. A jejunal segment was initially perfused with saline, followed by SP in saline, and finally perfused with saline alone. The regional blood flow to the small intestine was determined by the microsphere technique. Endoluminal perfusion with SP caused a selective mucosal/submucosal hyperaemia of the experimental jejunum, which was normalized upon subsequent saline perfusion. Since neither acute vagotomy, local neural blockade (TTX, lidocaine), adrenergic blockade (phenoxybenzamine, propranolol), cholinergic blockade (hexamethonium, atropine), histamine - nor prostaglandin blockade - could antagonize the hyperaemic effects of luminally administered SP, it is suggested that this effect is directly paracrine in nature. Substance P may be released from SP nerves on physiological stimulation, that is, augmented vagal tone by a meal, and act at the effector cell, that is, vascular smooth muscle.