Presynaptic beta-adrenoceptors in rat atria: evidence for the presence of stereoselective beta 1-adrenoceptors.

1. Presynaptic beta-adrenoceptor activity was studied in rat isolated atria, previously loaded with [3H]-noradrenaline. The stimulation-induced release of 3H transmitter was measured in the presence of cocaine, and adrenaline was used as a facilitatory beta-adrenoceptor agonist. 2. Adrenaline (0.1 and 2 nM) increased, by about 50%, the evoked efflux of tritium. With phenoxybenzamine present, the same activity was shown with 10 nM adrenaline. 3. The beta 2-selective adrenoceptor blocking drugs: IPS 339 and ICI 118 551 caused a concentration-dependent decrease in the activity of adrenaline. Cardioselective beta-blocking drugs: acebutolol, beta-xolol, nebivolol and its isomers (R 67 138 and R 67 145) also reduced dose-dependently the agonistic action of adrenaline. The order of potency for nebivolol and its isomers was R 67 138 greater than nebivolol greater than R 67 145. The activity of pindolol was not concentration-dependent. The inhibitory effect of acebutolol was also observed in the presence of blockade of alpha-adrenoceptors. 4. The postsynaptic beta-adrenoceptor blocking activity of nebivolol and its isomers was studied in pithed rats. They reduced isoprenaline-induced tachycardia without altering hypotensive responses. The order of potency was: R 67 138 greater than nebivolol greater than R 67 145. 5. It is concluded that in rat isolated atria, presynaptic beta 2- and beta 1-adrenoceptors coexist and that facilitatory beta 1-adrenoceptors are stereospecific.