Pertussis toxin does not attenuate alpha 2-adrenoceptor mediated inhibition of noradrenaline release in mouse atria.
1. The alpha 2-adrenoceptor agonist clonidine (0.03 and 0.1 mumol/l) significantly inhibited stimulation-induced overflow of radioactivity from mouse isolated atria preincubated with [3H]-noradrenaline. This effect of clonidine was blocked by idazoxan (0.3 mumol/l) but not prazosin (0.3 mumol/l), indicating that an alpha 2-adrenoceptor was involved. 2. In some experiments mice were injected with pertussis toxin (1.5 micrograms/mouse) 4 days before their atria were removed and subsequently incubated with [3H]-noradrenaline. Alternatively, isolated atria from untreated mice were suspended in Krebs-Henseleit solution, incubated for 16 h with pertussis toxin (1.0 and 4.0 micrograms/ml) or vehicle and subsequently incubated with [3H]-noradrenaline. The effectiveness of pertussis toxin pretreatment was assessed indirectly using carbachol. Carbachol caused a dose dependent fall in both the rate and force of contraction of isolated, spontaneously beating atria from mice pretreated with vehicle in vivo or in vitro. This effect of carbachol was not seen in atria from mice pretreated with pertussis toxin in vivo or in vitro, suggesting that active toxin penetrated the myocardium. 3. Pertussis toxin pretreatment, either in vivo or in vitro did not alter the inhibitory effect of clonidine (0.03 and 0.1 mumol/l), or the facilitatory effect of the alpha-adrenoceptor antagonist phentolamine (1.0 mumol/l), on the stimulation-induced overflow of radioactivity. These results suggest that alpha 2-adrenoceptor modulation of noradrenaline release from sympathetic nerve terminals is not dependent on an inhibitory guanine-nucleotide-binding protein.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D037342:Pertussis Toxin; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D002217:Carbachol; D037342:Pertussis Toxin; D009638:Norepinephrine