Identification and distribution of mRNA encoding the Y1, Y2, Y4, and Y5 receptors for peptides of the PP-fold family in the rat intestine and colon.

Peptide YY (PYY), neuropeptide Y (NPY) and pancreatic polypeptide (PP) are structurally related peptides which have potent antisecretory effects in small and/or large intestines. Receptors mediating these effects are still unknown with the exception of a PYY-preferring receptor expressed in small intestinal crypts. In the present study, expression of recently cloned Y1, Y2, and Y5 receptors which have similar affinity for PYY and NPY and Y4 receptors which have a high affinity for PP was investigated in gut by RT-PCR analysis. The data show that all Y receptors are expressed in small intestine and/or colon but with specific distributions. Y1 receptors are only expressed in nonepithelial colonic tissue, whereas Y2 and Y4 receptors are present in both epithelial and nonepithelial tissue of the small or large intestine. In contrast, Y5 receptor expression appears to be restricted to epithelial crypts of the small intestine and nonepithelial tissue of colon. Sequencing of PCR products showed 100% identity with the corresponding sequences of the cloned Y1, Y4, or Y5 receptors. The PCR product obtained with Y2 primers from rat crypt cells showed 84% identity with the cloned human Y2 receptor. These data indicate a wide distribution of Y receptors in small intestine and colon. They also suggest that Y1, Y2, Y4, and Y5 receptors may be responsible for still unexplained effects of PYY, NPY, or PP on secretion in small and large intestines.