Inhibitory effect of neuropeptide Y and its analogues on inositol 1,4,5-trisphosphate level in rat cardiomyocytes.

A negative inotropic effect of neuropeptide Y (NPY) in the mammalian heart has been reported. The mechanism(s) involved in the action of NPY in the heart is still unclear. Since D-myo-inositol 1,4,5-trisphosphate[Ins(1,4,5)P3] is known to be an important second messenger in the regulation of cardiac function, we carried out a study to investigate the status of Ins(1,4,5)P3 levels in response to NPY stimulation in rat cardiomyocytes. We also studied the possible involvement of NPY receptor subtypes in Ins(1,4,5)P3 formation. [Leu31, Pro34]NPY,NPY13-36, NPY and peptide YY (PYY) Induced a concentration-dependent decrease in Ins(1,4,5)P3 levels [measured with an Ins(1,4,5)P3 protein binding assay kit] in rat cardiomyocytes, which was blocked by NPY antagonists NPY18-36 or PYX-2. There is no difference in the inhibitory effect of NPY and PYY on Ins(1,4,5)P3 formation. Furthermore, effects of NPY and its analogues were insensitive to pertussis toxin pretreatment. Two new and more specific Y2 receptor agonists, [Ahx5-24]NPY and [Ahx5-24, gamma-Glu2-epsilon-Lys30]NPY, produced similar effects as NPY13-36 on Ins(1,4,5)P3 formation. These observations indicate that Y1 and Y2 subtypes of NPY receptor in rat cardiomyocytes may be associated with Ins(1,4,5)P3 formation through a pertussis-toxin-insensitive Gq protein. The decreased Ins(1,4,5)P3 formation may be implicated in the negative inotropic effect of NPY in the heart.