NEW ROLE OF NERVE GROWTH-FACTOR - AN INHIBITORY NEUROMODULATOR OF ADRENERGIC TRANSMISSION

In the present study, we investigated the effects of nerve growth factor (NGF) on norepinephrine (NE) release from peripheral sympathetic nerve endings of rat mesenteric artery. We made isolated mesenteric artery-intestinal loop preparations, by the modified method of Castelluci et al., from 4- and 8-week-old Wistar rats. NGF produced a dose-dependent inhibition of NE overflow from sympathetic nerve endings evoked by electrical nerve stimulation in the range of 0.1-10 ng/ml. Inhibition of NE overflow also occurred in the presence of a neuronal uptake blocker, desipramine (5 x 10(-8) M). NGF showed no effect on pressor response to exogenous NE (1-mu-g). These results suggest that NGF inhibits NE release from sympathetic nerve endings, in other words, NGF acts as an inhibitory neuromodulator of adrenergic transmission. This function of NGF might be considered as an inhibitory feedback mechanism against catecholamine-stimulated NGF synthesis.