A hitch-hiker's guide to the galaxy of adrenoceptors

Abstract

In view of the widespread ramifications of noradrenergic nerve terminals in many tissues and the far greater number of postganglionic noradrenergic neurones with which any one preganglionic nerve synapses sympathetic nerve activity might be expected to be associated with equally widespread effects—or, at least, more of the tissue might be expected to be influenced by the neurotransmitter than if the same number of parasympathetic postganglionic cholinergic neurones had been activated. Similarly, the complex biochemical changes so often associated with activation of adrenoceptors would be expected to produce changes in the cell function which would outlast the usual transient changes in membrane permeability associated with activation of cholinoceptors. Furthermore, the effects of adrenoceptor activation by noradrenaline acting as neurotransmitter can be reinforced by the action of circulating adrenaline and noradrenaline released from the adrenal medullae. On the other hand, several mechanisms operate locally to control the amount of noradrenaline released during repetitive activity at different rates of discharge of postganglionic sympathetic nerves. The intensity of action of the catecholamines (and of exogenously administered drugs used to mimic their effects) can be influenced by several factors including the number of available adrenoceptors mediating the responses observed. It has been known for many years that glucocorticoids need to be present for the full action of the catecholamines, but how these steroids play their permissive part is still to be resolved. Much of our knowledge of the pharmacology of adrenoceptors and of noradrenergic neurotransmission comes from investigations of sympathetically innervated tissues—because the junctions are more accessible for study than in the central nervous system. The mechanisms may not necessarily be the same within the central nervous system, where, for example, dopamine, noradrenaline, and adrenaline each act as neurotransmitter substances in different regions. The hope is that the information obtained from studies in the peripheral nervous system will be of value in advancing our understanding of a wide variety of disorders of the central nervous system and in unravelling physiological control mechanisms, such as those which operate to regulate arterial blood pressure. © 1981, British Medical Journal Publishing Group. All rights reserved.