Mu-opioid-receptor-mediated inhibition of the N-type calcium-channel current.
The predominant consequences of mu-opioid-receptor activation are depression of both neuronal activity and transmitter release. Mu-Opioid agonists have previously been observed to increase a potassium conductance and to inhibit adenylate cyclase. We now report that activation of mu-opioid receptors directly decreases the N-type calcium-channel current in a differentiated, human neuroblastoma cell line (SH-SY5Y). The coupling between the mu-opioid receptor and the calcium channel involves a pertussis toxin-sensitive G protein and is independent of changes in adenylate cyclase activity. The inhibition of the calcium-channel current is voltage dependent because it is largely overcome by strong membrane depolarization. It is not associated with changes in the kinetics of current inactivation. Therefore, the mu-receptor belongs to the superfamily of G-protein-coupled, inhibitory neurotransmitter receptors which modulate the activity of calcium and potassium channels and adenylate cyclase.
Department of Pharmacology, University of Cambridge, U.K.
E
E
Seward
C
C
Hammond
G
G
Henderson
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials; D009270:Naloxone / Q000494:pharmacology; D037342:Pertussis Toxin; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017450:Receptors, Opioid, mu; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D015220:Calcium Channels; D004745:Enkephalins; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D010566:Virulence Factors, Bordetella; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins