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-mu-Ci 7-[H-3]noradrenaline. In the presence of cocaine, 3 x 10(-6) mol 1(-1), and atropine, 10(-7) mol 1(-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 1(-1), or tyramine 10(-5) mol 1(-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 1(-1) tetrodotoxin. Pretreatment with 3 x 10(-7) mol 1(-1) idazoxan increased the effects of field stimulation, while they were attenuated in the presence of clonidine, 3 X 10(-7) mol 1(-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.