An inhibitory effect of isoprenaline on stimulation-induced noradrenaline release from rat atria

Abstract

Isoprenaline (0.1 μM), in the presence of phentolamine (1 μM) to block autoinhibitory α-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 [ 3H]noradrenaline. This facilitatory effect of isoprenaline on noradrenergic transmission was not affected by the selective β 1-adrenoceptor antagonist CGP 20712A (0.3 μM). However, the selective β 2-adrenoceptor antagonist ICI 118551 (0.1 μM) not only abolished the facilitatory effect of isoprenaline but reversed it to an inhibitory effect, indicating that the prejunctional β-adrenoceptors subserving facilitation of noradrenergic transmission in rat atria are of the β 2-subtype. The inhibitory effect of isoprenaline that was revealed by blockade of β 2-adrenoceptors was abolished by atenolol (3 μM) in a concentration which markedly reduced the effect of isoprenaline on the rate of atrial beating. This finding suggests that activation of β 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 μM) suggesting that prostaglandins were not involved.