Physiological and clinical relevance of endorphins

Abstract

Much progress has been made in recent years towards the understanding of the action of opiates. It was demonstrated by several groups (Pert and Snyder, 1973; Simon et al., 1973; Terenius, 1973) that the first step in the interaction between opiates and nervous tissue is the reversible binding to specific receptors in the synaptic plasma membranes. Following binding to the receptor the morphine-like opiates will inhibit adenylate cyclase activity (Collier et al., 1974; Sharma et al., 1975; Traber et al., 1975). The finding of specific opiate receptors and the coupling between receptor occupation and inhibition of adenylate cyclase activity, suggested the presence of a functional receptor unit. Since the opiate receptor proved to be extremely specific, having practically no affinity for previously known neurotransmitters or neuroactive agents, it seemed possible that such receptors might have previously unknown natural substrates, ligands. These considerations led to the search for such ligands in the brain and evidence for their existence was obtained (Hughes, 1975; Terenius and Wahlström, 1975a). Similarly, Cox, Goldstein and coworkers (1975) identified opiate-like material in the pituitary gland. The publication of the structure of the enkephalins (Hughes et al., 1975) led to extensive chemical work and it soon became clear, that in addition to the enkephalins, several other, higher-molecular weight peptides were opiate like (Bradbury et al., 1976; Guillemin et al., 1976; Li and Chung, 1976). These peptides are now collectively called endorphins (endogenous morphine-like agents).