RECEPTORS CONTROLLING TRANSMITTER RELEASE FROM SYMPATHETIC NEURONS IN VITRO

Abstract

Primary cultures of postganglionic sympathetic neurons were established more than 30 years ago. More recently, these cultures have been used to characterize various neurotransmitter receptors that govern sympathetic 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, depolarization-evoked release. Group (1) comprises nicotinic and muscarinic acetylcholine receptors, P 2X purinoceptors and pyrimidinoceptors. Group (2) currently harbours β-adrenoceptors, P 2 purinoceptors, receptors for PACAP and VIP, as well as prostanoid EP 1 receptors. In group (3), muscarinic cholinoceptors, α 2- and β-adrenoceptors, P 2 purinoceptors, and receptors for the neuropeptides NPY, somatostatin (SRIF 1) and LHRH, as well as opioid (δ and κ) receptors can be found. 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. Most of the receptors that evoke release are located at the soma. There, ionotropic receptors cause depolarizations to generate action potentials which then trigger Ca 2+-dependent exocytosis at axon terminals. The signalling mechanisms of metabotropic receptors which evoke release still remain to be identified. Receptors which facilitate depolarization-evoked release appear to be located preferentially at presynaptic sites and presumably act via an increase in cyclic AMP. Receptors which inhibit stimulation evoked release are also presynaptic origin and most commonly rely on a G protein-mediated blockade of voltage-gated Ca 2+ channels. Results obtained with primary cell cultures of postganglionic sympathetic neurons have now supplemented previous data about neurotransmitter receptors involved in the regulation of ganglionic as well 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. © 1997 Elsevier Science Ltd. All Rights Reserved.