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 s tudies have shown that neuropeptide Y inhibits coronary flow and exert s a negative inotropic effect in isolated perfused hearts and cardiac muscles. The mechanisms involved in the action of neuropeptide Y in th e heart are under active investigation. Our studies have been shown th at [Leu(31),Pro(34)]NPY, NPY13-36, neuropeptide Y and peptide YY induc ed a concentration-dependent decrease in inositol 1,4,5-trisphosphate levels in rat cardiomyocytes, which was blocked by neuropeptide Y anta gonists NPY18-36 or PYX-2. There is no difference in the inhibitory ef fect of neuropeptide Y and peptide YY on inositol 1,4,5-triphosphate f ormation. 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 c ardiomyocytes may be associated with inositol 1,4,5-triphosphate forma tion through a pertussis toxin-insensitive Gq protein. The decreased f ormation of inositol 1,4,5-triphosphate may be implicated in the negat ive inotropic effect of neuropeptide Y in the mammalian heart. In dogf ish hearts, on the other hand, neuropeptide Y increased cardiac output by increasing heart rate, whereas norepinephrine increased cardiac ou tput by increasing stroke volume. Although neuropeptide Y or norepinep hrine alone did not have significant effects on pressure development i n these hearts, neuropeptide Y plus norepinephrine did increase pressu re 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 neuropeptid e 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 he arts. 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 .