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 Y1/Y2 agonists, NPY and PYY, and the Y2 agonist, NPY13-36, elicited concentration-dependent contraction of circular muscle cells that was inhibited by the selective Y2 antagonist, BIIE 0246. The Y4 agonist, PP, elicited similar, though weaker, contraction that was insensitive to Y1 and Y2 antagonists. The Y1 agonist, [Leu31, Pro34]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 Y1/Y2 agonists, NPY and PYY, and the Y1 agonist, [Leu31, Pro34]NPY, inhibited cAMP formation and VIP-induced muscle cell relaxation. 125I-PYY binding in longitudinal muscle cells was inhibited by NPY, PYY, [Leu31, Pro34]NPY and the Y1 antagonist, BIBP 3226. Contraction of circular but not longitudinal muscle cells by Y2 and Y4 agonists was observed also in cells isolated from human jejunum. The results indicate that Y2 and Y4 receptors are present only in intestinal circular muscle cells where they mediate contraction that is insensitive to PTx or Ca2+ channel blockers. Y1 receptors, negatively coupled to adenylyl cyclase, are present in cells from both layers.