No influence of prejunctional alpha 2-adrenoceptors on the effects of nicotine and tyramine in guinea-pig atria.
1. Guinea-pig left atria were stimulated at a rate of 0.5 Hz and preloaded with 10 microCi 7-[3H]noradrenaline. In the presence of cocaine, 3 x 10(-6) mol l-1, and atropine, 10(-7) mol l-1, noradrenaline release was stimulated twice in each atrium, either by electrical field stimulation (one pulse, 0.2 ms 30 V, during each refractory period for 5 min) or by addition of either nicotine, 3 x 10(-5) mol l-1, or tyramine 10(-5) mol l-1. 2. The release of radioactivity caused by field stimulation and the associated positive inotropic effect were almost abolished by 3 x 10(-8) mol l-1 tetrodotoxin. Pretreatment with 3 x 10(-7) mol l-1 idazoxan increased the effects of field stimulation, while they were attenuated in the presence of clonidine, 3 x 10(-7) mol l-1. 3. The inotropic effect and the release of radioactivity caused by nicotine were greatly attenuated by tetrodotoxin, but were not significantly influenced by idazoxan or clonidine. 4. The release of radioactivity caused by tyramine and the inotropic effect of this drug were resistant to tetrodotoxin pretreatment and were not modified by idazoxan or clonidine. 5. It is concluded that nicotine releases noradrenaline by initiating a propagated action potential. But activation of prejunctional alpha 2-adrenoceptors does not seem to attenuate the transmitter release by limiting the spread of the action potential in the prejunctional sympathetic neuronal network.
Department of Pharmacology, Medical University of Lübeck, Germany.
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Brasch
D000200:Action Potentials / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D019329:Idazoxan; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D013779:Tetrodotoxin; D009538:Nicotine; D003000:Clonidine; D014439:Tyramine; D019329:Idazoxan