Effect of calcium channel blockers on norepinephrine release and modulation by prejunctional D2 dopamine receptors.
Influx of calcium through voltage-dependent N-type calcium channels promotes the release of norepinephrine from nerve terminals. Contributions by L- and N-type calcium channels at different levels of nerve stimulation were examined in perfused rat tail arteries loaded with [3H]norepinephrine. Nifedipine had no effect while omega-conotoxin reduced tritium efflux by 69 to 82% depending on the stimulation intensity. Thus, N-type calcium channels predominated in the control of norepinephrine release, and the relative contribution of L- and N-type channels did not change when stimulation intensity was altered. We also explored the effect of calcium channel blockers on modulation of norepinephrine release by D2 dopamine receptors. Inhibition of stimulation-evoked tritium efflux by the D2 agonist N-0923 was similar in the absence and presence of nifedipine and/or omega-conotoxin. We conclude that D2 dopamine receptors are not coupled to L-type calcium channels; however, the role of N-type calcium channels requires further investigation.
Friedman
D J
DJ
Department of Pharmacology, College of Medicine, University of California, Irvine 92717.
Duckles
S P
SP
D000818:Animals; D001158:Arteries / Q000294:innervation*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D004558:Electric Stimulation; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D015259:Dopamine Agents; D010455:Peptides; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D020960:omega-Conotoxins; C053423:Conus magus toxin; C047508:rotigotine; D009543:Nifedipine; D009638:Norepinephrine