AN INHIBITORY EFFECT OF ISOPRENALINE ON STIMULATION-INDUCED NORADRENALINE RELEASE FROM RAT ATRIA

Isoprenaline (0.1-mu-M), in the presence of phentolamine (1-mu-M) to block autoinhibitory alpha-adrenoceptors, significantly increased the efflux of radioactivity produced by field stimulation (2 Hz for 60 s) from rat isolated atria in which the noradrenergic transmitter stores had been labelled with [H-3]noradrenaline. This facilitatory effect of isoprenaline on noradrenergic transmission was not affected by the selective beta-1-adrenoceptor antagonist CGP 20712A (0.3-mu-M). However, the selective beta-2-adrenoceptor antagonist ICI 118551 (0.1-mu-M) not only abolished the facilitatory effect of isoprenaline but reversed it to an inhibitory effect, indicating that the prejunctional beta-adrenoceptors subserving facilitation of noradrenergic transmission in rat atria are of the beta-2-subtype. The inhibitory effect of isoprenaline that was revealed by blockade of beta-2-adrenoceptors was abolished by atenolol (3-mu-M) in a concentration which markedly reduced the effect of isoprenaline on the rate of atrial beating. This finding suggests that activation of beta-1-adrenoceptors on atrial myocytes by isoprenaline may have resulted in release of one or more substance(s) which inhibited stimulation-induced release of noradrenaline, presumably by activating prejunctional receptors. The inhibitory effect of isoprenaline on noradrenergic transmission was not affected by the prostaglandin synthesis inhibitor indomethacin (10-mu-M) suggesting that prostaglandins were not involved.