Regulation of release and function of neuropeptides in the heart.

The mechanisms regulating the release of enkephalins and neuropeptide Y (NPY) from cardiac nerve fibers were studied in the isolated perfused guinea pig heart. Besides NPY, all peptides of the proenkephalin B family were found to be stored in the adrenergic nerve endings. Following electrical stimulation of the accelerans nerve, but not of the vagus nerve, the peptides were detected in the perfusate indicating their release from sympathetic nerve endings. The release of both enkephalins and NPY was enhanced by phentolamine or yohimbine and diminished by cocaine. Thus, sympathetic amines may directly regulate the release of their cotransmitters via a presynaptic alpha-adrenergic mechanism. Enkephalins exerted a weak negative inotropic effect that appeared to be mediated by opioid receptors of the kappa type. Neuropeptide Y is a potent vasoconstrictor and may be involved in the regulation of coronary blood flow.