Prejunctional alpha 2-adrenoceptors in mouse atria function through G-proteins which are sensitive to N-ethylmaleimide, but not pertussis toxin.
1. The identity of the G-proteins involved in prejunctional alpha 2-adrenoceptor signal transduction in mouse atria was examined by use of the G-protein inactivators N-ethylmaleimide and pertussis toxin. 2. The alpha 2-adrenoceptor partial agonist clonidine (0.03 microM) inhibited the electrical stimulation-induced (S-I) outflow of radioactivity from mouse atria which were incubated with [3H]-noradrenaline and stimulated at 5 Hz. The partial alpha 2-adrenoceptor agonist St 363 (10 microM) inhibited the S-I outflow of radioactivity at the lower stimulation frequency of 2.5 Hz. The inhibitory effects of these compounds were not altered in mice pretreated with pertussis toxin (1.5 micrograms, i.v.). 3. The alpha 2-adrenoceptor antagonist, idazoxan (0.1 microM), increased the S-I outflow of radioactivity from mouse atria stimulated at 5 Hz, and this effect was not altered in atria from mice pretreated with pertussis toxin. 4. The inhibitory effects of clonidine and St 363 and the facilitatory effect of idazoxan on the S-I outflow of radioactivity from mouse atria were significantly less in atria incubated with N-ethylmaleimide (NEM, 3 microM) for 60 min before the [3H]-noradrenaline incubation. 5. The results suggest that prejunctional alpha 2-adrenoceptors in mouse atria function through G-proteins which are NEM-sensitive, but pertussis toxin insensitive.
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
T V
TV
Murphy
S
S
Foucart
H
H
Majewski
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D016275:Atrial Function; D002217:Carbachol / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology*; D005260:Female; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D009638:Norepinephrine / Q000032:analysis; D037342:Pertussis Toxin; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D014316:Tritium; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D014316:Tritium; D002217:Carbachol; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D005033:Ethylmaleimide; D009638:Norepinephrine