ADRENOCEPTOR-MEDIATED EFFECT OF NEUROPEPTIDE-Y DECREASES CARDIAC INOTROPIC RESPONSES

The effect of neuropeptide Y on the number and affinity of catecholami ne receptors in the ventricular myocardium was investigated. Receptor binding studies showed that incubation of cardiac membrane in the pres ence of neuropeptide Y (NPY, 10(-7) M) decreased the number of alpha,b eta-adrenoceptor binding sites (B-max) without affecting the affinity (K-D) of these receptors. Although not able to modulate the contractil ity by itself, NPY was able to decrease the positive inotropic effects of phenylephrine and isoproterenol in the isolated, perfused myocardi um. Ca2+/Mg2+-ATPase activity, measured from the sarcolemma, sarcoplas mic reticulum and myofibrils, was unaltered whereas the activity of sa rcolemmal Na+/K+-ATPase was decreased when NPY was included in the med ia. On the other hand, NPY was shown to increase the phosphoinositide- phospholipase C associated with the sarcolemma. These findings support the hypothesis that NPY modulates postsynaptic adrenergic receptors i n the myocardium and can affect the adrenergic-induced, inotropic resp onse.