Presynaptic β‐adrenoceptors in rat atria: evidence for the presence of stereoselective β 1 ‐adrenoceptors

1 Presynaptic β‐adrenoceptor activity was studied in rat isolated atria, previously loaded with [ 3 H]‐noradrenaline. The stimulation‐induced release of 3 H transmitter was measured in the presence of cocaine, and adrenaline was used as a facilitatory β‐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 β 2 ‐selective adrenoceptor blocking drugs: IPS 339 and ICI 118 551 caused a concentration‐dependent decrease in the activity of adrenaline. Cardioselective β‐blocking drugs: acebutolol, betaxolol, 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 > nebivolol > 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 α‐adrenoceptors. 4 The postsynaptic β‐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 > nebivolol > R 67 145. 5 It is concluded that in rat isolated atria, presynaptic β 2 ‐ and β 1 ‐adrenoceptors coexist and that facilitatory β 1 ‐adrenoceptors are stereospecific.