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 the novel member of the opioid family, nociceptin/orphanin FQ, inhibit the spontaneous electrical activity of neurons recorded from the rostral ventrolateral medulla, presumably cardiovascular neurons. In this study, the putative effects of endomorphin-1 and endomorphin-2, the newly discovered endogenous ligands for the micro-opioid receptor, on the electrical activity of rostral ventrolateral medulla neurons were investigated in rat brain slices in vitro. Like enkephalin and nociceptin, perfusion of endomorphin-1 or endomorphin-2 profoundly inhibited spontaneous discharges of 43% and 38% of the medullary neurons, respectively. No excitatory response to perfusion of either endomorphin was found in all neurons surveyed. Both endomorphins produced concentration-dependent inhibition. However, endomorphin-1 was more potent than endomorphin-2 for production of the inhibition, as demonstrated by the greater and longer suppression induced by endomorphin-1 than that induced by endomorphin-2 at the same concentration. Among the four opioid agonists tested, EC50 values (in nM) were 3.17 (endomorphin-1), 3.02 (nociceptin), 10.1 (endomorphin-2) and 150.0 (enkephalin). The non-selective opioid receptor antagonist, naloxone, blocked the inhibitory responses of the neurons to endomorphin-1, endomorphin-2 and enkephalin, but not to nociceptin. The selective mu antagonist, beta-funaltrexamine, prevented the neuronal inhibition induced by endomorphins, but not by enkephalin and nociceptin. Neither naloxone nor beta-funaltrexamine alone had a significant effect on the firing rate of the neurons. These results demonstrate that endomorphin-1 and, to a lesser extent, endomorphin-2 exert an inhibitory modulation of the electrical activity of rostral ventrolateral medulla neurons, which is mediated through the stimulation of mu-opioid receptors.
Chu
X P
XP
Department of Physiology, Shanghai Medical University, People's Republic of China.
Xu
N S
NS
Li
P
P
Wang
J Q
JQ
D000818:Animals; D004594:Electrophysiology; D004744:Enkephalin, Methionine / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology* / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000502:physiology*; D000097629:Nociceptin
D004744:Enkephalin, Methionine; D008024:Ligands; D009270:Naloxone; D009271:Naltrexone; D009292:Narcotic Antagonists; D009842:Oligopeptides; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; D000097629:Nociceptin; C105293:endomorphin 1; C105294:endomorphin 2; C024524:beta-funaltrexamine