Characterization of two 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 intestinal extracts of several mammalian species including pig, rat, dog, and man. The primary structure of rabbit PYY is still unknown, although rabbit tissues have extensively been used for characterization of PYY 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 YPSKPEAPGEDASPEELNRYYASLRHYLNLVTRQRY-amide. Rabbit PYY differs from porcine 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 forms of PYY in the rabbit, with PYY-II lacking the amino-terminal dipeptide 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 Y1/Y2 agonist, whereas PYY-II is a highly selective Y2 agonist. Thus, proteolytic processing of PYY-I controls the peptide's receptor selectivity. The existence of PYY-I and PYY-II in the rabbit supports the assumption of a physiological role of Y receptor heterogeneity for PYY.