Differential expression of Y receptors and signaling pathways in intestinal circular and longitudinal smooth muscle

The expression and mechanisms of action of Y receptors were examined in dispersed intestinal smooth muscle cells of the rabbit. The mixed Y 1/Y 2 agonists, NPY and PYY, and the Y 2 agonist, NPY 13–36, elicited concentration-dependent contraction of circular muscle cells that was inhibited by the selective Y 2 antagonist, BIIE 0246. The Y 4 agonist, PP, elicited similar, though weaker, contraction that was insensitive to Y 1 and Y 2 antagonists. The Y 1 agonist, [Leu 31, Pro 34]NPY, did not elicit contraction of circular muscle cells. All Y receptor agonists inhibited cAMP formation in a PTx-sensitive fashion. In contrast, none of the agonists caused contraction of longitudinal muscle cells, and only the mixed Y 1/Y 2 agonists, NPY and PYY, and the Y 1 agonist, [Leu 31, Pro 34]NPY, inhibited cAMP formation and VIP-induced muscle cell relaxation. 125I-PYY binding in longitudinal muscle cells was inhibited by NPY, PYY, [Leu 31, Pro 34]NPY and the Y 1 antagonist, BIBP 3226. Contraction of circular but not longitudinal muscle cells by Y 2 and Y 4 agonists was observed also in cells isolated from human jejunum. The results indicate that Y 2 and Y 4 receptors are present only in intestinal circular muscle cells where they mediate contraction that is insensitive to PTx or Ca 2+ channel blockers. Y 1 receptors, negatively coupled to adenylyl cyclase, are present in cells from both layers.