Neuropeptide Y and sympathetic neurotransmission.

The coexistence of neuropeptide Y (NPY) with noradrenaline (NA) in perivascular nerves as well as in sympathetic nerves to muscle in the heart, spleen and vas deferens suggests a role for NPY in autonomic transmission. Sympathetic nerve stimulation or reflexogenic activation in experimental animals or man are associated with NPY release as revealed by overflow mainly upon strong activation. This difference between NPY and NA secretion may be related to the partly separate subcellular storage whereby NPY seems to be exclusively present in the large dense-cored vesicles. The NPY secretion is likely to be regulated by the local biophase concentrations of NA acting on prejunctional alpha-2-adrenoceptors since alpha-2 agonists inhibit and antagonists enhance NPY overflow, respectively. Furthermore, after NA has been depleted by reserpine, the nerve stimulation-evoked release of NPY is enhanced leading to a progressive depletion of tissue content of NPY. Exogenous NPY binds to both pre- and postjunctional receptors, inhibits NA and NPY release, enhances NA-evoked vasoconstriction and induces vasoconstriction per se. The prejunctional action of NPY which is especially noticeable in the vas deferens may serve to reduce transmitter secretion upon excessive stimulation. The long-lasting vasoconstriction evoked by sympathetic stimulation in several tissues including skeletal muscle, nasal mucosa and spleen, which remains in animals pretreated with reserpine (to deplete NA) combined with preganglionic denervation (to prevent the concomitant excessive NPY release and depletion), is mimicked by NPY and highly correlated to NPY release. Under these circumstances the NPY content in the local venous effluent reaches levels at which exogenous NPY evokes vasoconstriction.