COMPARATIVE ASPECTS OF THE ROLE OF NEUROPEPTIDE-Y IN THE REGULATION OF THE VERTEBRATE HEART

The role of neuropeptide Y (NPY) in the regulation of cardiac function was compared in mammalian and fish hearts. In mammalian heart, most studies have shown that neuropeptide Y inhibits coronary flow and exerts a negative inotropic effect in isolated perfused hearts and cardiac muscles. The mechanisms involved in the action of neuropeptide Y in the heart are under active investigation. Our studies have been shown that [Leu(31),Pro(34)]NPY, NPY13-36, neuropeptide Y and peptide YY induced a concentration-dependent decrease in inositol 1,4,5-trisphosphate levels in rat cardiomyocytes, which was blocked by neuropeptide Y antagonists NPY18-36 or PYX-2. There is no difference in the inhibitory effect of neuropeptide Y and peptide YY on inositol 1,4,5-triphosphate formation. Furthermore, the effects of neuropeptide Y and its analogues were insensitive to pertussis toxin pretreatment. These observations indicate that Y-1 and Y-2 subtypes of neuropeptide Y receptor in rat cardiomyocytes may be associated with inositol 1,4,5-triphosphate formation through a pertussis toxin-insensitive Gq protein. The decreased formation of inositol 1,4,5-triphosphate may be implicated in the negative inotropic effect of neuropeptide Y in the mammalian heart. In dogfish hearts, on the other hand, neuropeptide Y increased cardiac output by increasing heart rate, whereas norepinephrine increased cardiac output by increasing stroke volume. Although neuropeptide Y or norepinephrine alone did not have significant effects on pressure development in these hearts, neuropeptide Y plus norepinephrine did increase pressure development. The inositol 1,4,5-triphosphate level was elevated by norepinephrine alone and was further increased by neuropeptide Y plus neuropeptide Y plus norepinephrine. The data indicate that neuropeptide Y could potentiate the effect of norepinephrine in the dogfish heart, and the changes in inositol 1,4,5-triphosphate may be implicated in the cardiac effects of neuropeptide Y and norepinephrine in dogfish hearts. In summary, neuropeptide Y is involved in the control of cardiac function in both mammalian and fish hearts and the effect appears to be mediated by the intracellular messenger inositol 1,4,5-triphosphate.