RECEPTORS CONTROLLING TRANSMITTER RELEASE FROM SYMPATHETIC NEURONS IN-VITRO

Primary cultures of postganglionic sympathetic neurons were establishe d more than 30 years ago. More recently, these cultures have been used to characterize Various neurotransmitter receptors that govern sympat hetic transmitter release. These receptors may be categorized into at least three groups: (1) receptors which evoke transmitter release; (2) receptors which facilitate; (3) receptors which inhibit, depolarizati on-evoked release. Group (1) comprises nicotinic and muscarinic acetyl choline receptors, P(2)X purinoceptors and pyrimidinoceptors. Group (2 ) currently harbours beta-adrenoceptors, P-2 purinoceptors, receptors for PACAP and VIP, as well as prostanoid EPI receptors. In group (3), muscarinic cholinoceptors, alpha(2)- and beta-adrenoceptors, P-2 purin oceptors, and receptors for the neuropeptides NPY, somatostatin (SRIF( 1)) and LHRH, as well as opioid (delta and kappa) receptors can be fou nd. Receptors which regulate transmitter release from neurons in cell culture may be located either at the somatodendritic region or at the sites of exocytosis, i.e. the presynaptic specializations of axons. Mo st of the receptors that evoke release are located at the soma. There, ionotropic receptors cause depolarizations to generate action potenti als which then trigger Ca2+-dependent exocytosis at axon terminals. Th e signalling mechanisms of metabotropic receptors which evoke release still remain to be identified. Receptors which facilitate depolarizati on-evoked release appear to be located preferentially at presynaptic s ites and presumably act via an increase in cyclic AMP. Receptors which inhibit stimulation evoked release are also presynaptic origin and mo st commonly rely on a G protein-mediated blockade of voltage-gated Ca2 + channels. Results obtained with primary cell cultures of postganglio nic sympathetic neurons have now supplemented previous data about neur otransmitter receptors involved in the regulation of ganglionic as wel l as sympatho-effector transmission. In the future, this technique may prove useful to identify yet unrecognized receptors which control the output of the sympathetic nervous system and to elucidate underlying signalling mechanisms. (C) 1997 Elsevier Science Ltd.