ANTISECRETORY MECHANISMS OF PEPTIDE YY IN RAT DISTAL COLON

Peptide YY (PW) is a potent regulator of intestinal secretion. These s tudies investigated the role of Y1 and Y2 receptor subtypes in mediati ng the antisecretory effects of PW on mucosa-submucosa preparations of rat distal colon. Addition of vasoactive intestinal peptide (VIP) to these tissues resulted in a 140 +/- 18% increase in basal short-circui t current (I-SC) and the induction of Cl- secretion. VIP-stimulated in creases in I-SC were abolished by the addition of each of PW, (Pro(34) )-PYY, a Y1 receptor-selective agonist, and PYY-(3-36), an endogenous Y2 receptor-selective ligand. However, when tissue neural transmission was blocked with tetrodotoxin, neither PW nor its receptor subtype-se lective analogs were able to inhibit VIP-stimulated increases in I-SC. These results suggest that in the rat distal colon, the antisecretory actions of PW are mediated through a combination of Y1 and Y2 recepto r subtypes or through a novel receptor subtype that is unable to discr iminate between (Pro(34))-PYY and PYY-(3-36).