A possible mechanism for the release of serotonin from the gut caused by pentagastrin.
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.
Grönstad
K O
KO
Department of Surgery I, Gothenburg University, Sweden.
Ahlund
L
L
Dahlström
A
A
Häggendal
J
J
Ahlman
H
H
D000818:Animals; D001696:Biomechanical Phenomena; D002395:Catecholamines / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism*; D010418:Pentagastrin / Q000494:pharmacology*; D011169:Portal Vein; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D014682:Vena Cava, Inferior
D002395:Catecholamines; D012701:Serotonin; D010418:Pentagastrin