EXOCYTOTIC RELEASE FROM NEURONAL CELL-BODIES, DENDRITES AND NERVE-TERMINALS IN SYMPATHETIC-GANGLIA OF THE RAT, AND ITS DIFFERENTIAL REGULATION

Stimulant-induced exocytosis has been demonstrated in sympathetic gang lia of the rat by in vitro incubation of excised ganglia in the presen ce of tannic acid, which stabilizes vesicle cores after their exocytot ic release. Sites of exocytosis were observed along non-synaptic regio ns of the surfaces of neuron somata and dendrites, including regions o f dendrosomatic and dendrodendritic apposition, as well as along the s urfaces of nerve terminals. About half the exocytoses associated with nerve terminals were parasynaptic or synaptic, and these appeared most ly to arise from the presynaptic terminal, but occasionally from the p ostsynaptic element. The results demonstrated that the neurons of symp athetic ganglia release materials intraganglionically in response to s timulation, that release from different parts of the neuron is subject to independent regulation, at least via cholinergic receptors, and th at release is partly diffuse, potentially mediating autocrine or parac rine effects, and partly targeted toward other neurons, but that the l atter mode is not necessarily, and not evidently, synaptic. Specifical ly, exocytosis from ail locations increased significantly during incub ation in modified Krebs' solution containing 56 mM potassium. Observat ion of the effects of cholinergic agonists (nicotine, carbachol, oxotr emorine) and antagonists (atropine, AF-DX 116) showed that nicotinic a nd muscarinic excitation each, independently, increased the incidence of exocytosis from somata and dendrites. Exocytosis from nerve endings was not altered by nicotine, but was enhanced or, al high initial rat es of exocytosis, decreased, by muscarinic stimulation. Evidence was o btained for muscarinic auto-inhibition of exocytosis From nerve termin als, occurring under basal incubation conditions, and for a muscarinic excitatory component of somatic exocytosis, elicitable by endogenous acetylcholine. The M-2-selective muscarinic antagonist AF-DX 116 was f ound to modify the exocytotic response of the dendrites to oxotremorin e, widening the range of its variation; this effect is consistent with recent evidence for the presence of M-2-like muscarinic binding sites , in addition to M-1-like binding, upon these dendrites [Ramcharan E. J. and Matthews M. R. (1996) Neuroscience 71, 797-832]. Over all condi tions, disproportionately more sites of somatic and dendritic exocytos is were found to be located in regions of dendrosomatic and dendrodend ritic apposition than would be expected from the relative extent of th e neuronal surface occupied by these relationships. Such mechanisms of intraganglionic release may be expected to contribute to the regulati on and integration of the behaviour of the various functionally distin ctive populations of neurons in these ganglia, by autocrine, paracrine , and focal, neuroneuronal, routes of action. Similar phenomena of exo cytotic soma-dendritic release might prove to subserve integrative neu roneuronal interactions more widely throughout the nervous system. (C) 1997 IBRO. Published by Elsevier Science Ltd.