Mechanism of inhibition of calcium channels in rat nucleus tractus solitarius by neurotransmitters.
1. High-threshold Ca2+ channel currents were measured every 15 s following a 200 ms voltage step from -80 mV to 0 mV in order to study the coupling mechanism between neurotransmitter receptors and Ca2+ channels in neurones acutely isolated from the nucleus tractus solitarius (NTS) of the rat. 2. Application of 30 microM baclofen (GABAB receptor agonist) caused 38.9 +/- 1.2% inhibition of the peak inward Ba2+ current (IBa2+) in most NTS cells tested (n = 85 of 88). Somatostatin, 300 nM, also reduced IBa2+ by 31.3 +/- 1.6% in 53 cells of 82 tested. 3. Activation of mu-opioid-, GABAB- or somatostatin-receptors inhibited both N- and P/Q-type Ca2+ channels. 4. The inhibition of Ca2+ currents by DAMGo (mu-opioid receptor agonist), baclofen and somatostatin was reduced by treatment with pertussis toxin and partially relieved by application of a 50 ms conditioning prepulse to +80 mV. This suggests that a pertussis toxin-sensitive G-protein was involved in the neurotransmitter-mediated action in the observed inhibition of Ca2+ currents. 5. Intracellular loading with an antiserum raised against the amino terminus of Go alpha (GC/2) markedly attenuated the somatostatin-induced inhibition, but did not block the DAMGO- and baclofen-induced inhibition. 6. These findings suggest at least two different pertussis toxin-sensitive G-protein-mediated pathways are involved in receptor-induced inhibition of Ca2+ currents in the NTS.
Rhim
H
H
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637, USA.
Toth
P T
PT
Miller
R J
RJ
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002460:Cell Line; D004594:Electrophysiology; D018755:GABA Agonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D019204:GTP-Binding Proteins / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009292:Narcotic Antagonists; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D006727:Hormone Antagonists; D009292:Narcotic Antagonists; D018377:Neurotransmitter Agents; D011957:Receptors, Opioid; D010566:Virulence Factors, Bordetella; D013004:Somatostatin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D001418:Baclofen