Opioid biology: the next set of questions

Abstract

A range of biologically different opioid peptides are synthesised as components of three distinct precursors, pro-opiomelanocortin, proenkephalin, and prodynorphin. They interact with a number of receptors which have so far been characterised as mu, delta, kappa, sigma, and epsilon. It is unclear which ligands bind to which receptors under physiological circumstances, but preferential in vitro interactions include enkephalins with delta receptors, dynorphin with kappa receptors, and beta-endorphin with epsilon receptors. Post-translational processing determines which of several opioid products are produced from each precursor, but the identity of the enzymes involved and regulation of processing is unknown. Opioid involvement in the neuroendocrine and cardiovascular systems is reviewed. Naloxone-sensitive opioid mechanisms are implicated in the control of gonadotrophin and adrenocorticotropic hormone secretion and in the hypotension of various types of shock. The investigation of possible dynorphin involvement in neurohypophysial function is taking place because vasopressin and dynorphin A (1-8) have been shown to coexist in the neurosecretory vesicles of magnocellular neurons.