Electrophysiological effects of dermorphin on locus coeruleus neurons of rat.
Intracellular recording was used to study the effects of dermorphin on neurons of the locus coeruleus in the rat, in a totally submerged brain slice preparation. Dermorphin caused the inhibition of spontaneous firing of all neurons of the locus coeruleus tested, with an IC50 of 7 nM. Based on the inhibition of spontaneous firing rate, dermorphin was 16.5 times more potent than morphine. Larger concentrations of dermorphin (30-100 nM) further hyperpolarized the neurons of the locus coeruleus and simultaneously caused a reduction in input resistance. These effects were antagonized by naloxone, with a dissociation equilibrium constant of 0.8 nM. The hyperpolarization of neurons of the locus coeruleus, caused by dermorphin, was reversed at a membrane potential of -112 mV in this preparation. Furthermore, this hyperpolarization was blocked by cesium chloride and barium chloride. Thus, these data suggest that dermorphin binds to mu-opioid receptors on the cell membrane of neurons of the locus coeruleus. This leads to opening of the inward-going rectification potassium channels, resulting in the observed hyperpolarization of the membrane.
Chiu
T H
TH
Department of Physiology, National Yang-Ming Medical College, Taipei, R.O.C.
Chen
T Y
TY
Ho
C L
CL
Chiang
S T
ST
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001464:Barium / Q000494:pharmacology; D017609:Barium Compounds; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007700:Kinetics; D008125:Locus Coeruleus / Q000166:cytology* / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018847:Opioid Peptides; D051381:Rats; D011919:Rats, Inbred Strains
D000701:Analgesics, Opioid; D017609:Barium Compounds; D002712:Chlorides; D009842:Oligopeptides; D018847:Opioid Peptides; C024986:barium chloride; D002586:Cesium; D001464:Barium; C030058:dermorphin; D009270:Naloxone; D009020:Morphine; C028019:cesium chloride