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

摘要

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. (125)I-PYY binding in longitudinal muscle cells was inhibited by NPY, PYY, [Leu(31), Pro(34)]NPY and the Y(1) antagonist, BIBP 3226. Contractionof 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.