Endomorphin-1 and endomorphin-2, endogenous ligands for the mu-opioid receptor, inhibit electrical activity of rat rostral ventrolateral medulla neurons in vitro

The classic opioid peptide, enkephalin, and I:he novel member of the opioid family, nociceptin/orphanin FQ, inhibit the spontaneous electrical activit y of neurons recorded from the rostral ventrolateral medulla, presumably ca rdiovascular neurons. In this study, the putative effects of endomorphin-1 and endomorphin-2, the newly discovered endogenous ligands for the mu-opioi d receptor, on the electrical activity of rostral ventrolateral medulla neu rons were investigated in rat brain slices in vitro. Like enkephalin and no ciceptin, perfusion of endomorphin-1 or endomorphin-2 profoundly inhibited spontaneous discharges of 43% and 38% of the medullary neurons, respectivel y. No excitatory response to perfusion of either endomorphin was found in a ll neurons surveyed. Both endomorphins produced concentration-dependent inh ibition. However, endomorphin-1 was more potent than endomorphin-2 for prod uction of the inhibition, as demonstrated by the greater and longer suppres sion induced by endomorphin-1 than that induced by endomorphin-2 at the sam e concentration. Among the four opioid agonists tested, EC50 values (in nM) were 3.17 (endomorphin-1), 3.02 (nociceptin), 10.1 (endornorphin-2) and 15 0.0 (enkephalin). The non-selective opioid receptor antagonist, naloxone, b locked the inhibitory responses of the neurons to endomorphin-1, endomorphi n-2 and enkephalin, but not to nociceptin. The selective mu antagonist, bet a-funaltrexamine, prevented the neuronal inhibition induced by endomorphins , but not by enkephalin and nociceptin. Neither naloxone nor beta-funaltrex amine alone had a significant effect on the firing rate of the neurons. These results demonstrate that endomorphin-1 and, to a lesser extent, endom orphin-2 exert an inhibitory modulation of the electrical activity of rostr al ventrolateral medulla neurons, which is mediated through the stimulation of mu-opioid receptors. (C) 1999 IBRO. Published by Elsevier Science Ltd.