CHARACTERIZATION OF 2 FORMS OF PEPTIDE-YY, PYY(1-36) AND PYY(3-36), IN THE RABBIT

Peptide YY (PYY) has been purified as a 36 amino acid peptide from int estinal extracts of several mammalian species including pig, rat, dog, and man. The primary structure of rabbit PYY is still unknown, althou gh rabbit tissues have extensively been used for characterization of P YY receptor subtypes and receptor subtype-mediated actions. We report the purification and primary structure of PYY(1-36)(PYY-I) from rabbit intestinal mucosa, and the existence of a second endogenous molecular form of PYY, PYY(3-36)(PYY-II). The amino acid sequence of PYY-I is Y PSKPEAPGEDASPEELNRYYASLRHYLNLVTROQRY-amide. Rabbit PYY differs from po rcine PYY, which is identical to rat and canine PYY, by two amino acid substitutions at positions 3 (Ser instead of Ala) and 18 (Asp instead of Ser), whereas rabbit PYY and human PYY differ by only one residue at position 3 (Ser instead of Ile). The existence of two endogenous fo rms of PYY in the rabbit, with PYY-II lacking the amino-terminal dipep tide Tyr-Pro of PYY-I, is consistent with previously reported findings , demonstrating the existence of PYY-II in man and dog (9,11). We have previously demonstrated that PYY-I is an unselective Y-1/Y-2 agonist, whereas PYY-II is a highly selective Y-2 agonist. Thus, proteolytic p rocessing of PYY-I controls the peptides receptor selectivity. The exi stence of PYY-I and PYY-II in the rabbit supports the assumption of a physiological role of Y receptor heterogeneity for PYY.