Antisecretory effect of peptide YY through neural receptors in the rat jejunum in vitro.

Basal short circuit current (Isc) was measured in stripped rat jejunum after addition of neural antagonists and of peptide YY (PYY). Basal Isc was slightly (by 10-21%) but significantly inhibited by tetrodotoxin, hexamethonium, idazoxan, and the sigma antagonist BMY 14,802. PYY (10(-7) M) reduced basal Isc by approximately 54%. This inhibition was unchanged by hexamethonium but reduced by 44-68% in the presence of tetrodotoxin, idazoxan, haloperidol, BMY 14,802, and atropine. The Y2 agonist pYY(3-36) was more potent than the Y1 agonist (Leu31,Pro34)PYY. In conclusion, PYY reduces basal Isc in rat jejunum in part through a neural mechanism involving muscarinic receptors, alpha2 adrenoceptors, and sigma receptors and, in part, through a direct effect on enterocytes. The PYY effect seems mainly carried out through Y2-receptor activation.