Enhancement of noradrenaline release by angiotensin II and bradykinin in mouse atria: evidence for cross-talk between G(q/11) protein- and G(i/o) protein-coupled receptors

1 The interaction between alpha(2)-autoreceptors and receptors for angioten sin (AT(1)) and bradykinin (B-2) was studied in mouse isolated atria. The p reparations were labelled with [H-3]-noradrenaline and then superfused with desipramine-containing medium and stimulated electrically. 2 Angiotensin II (10(-11)-10(-7) M), angiotensin III (10(-10)-10(-6) M) and bradykinin (10(-11)-10(-7) M) enhanced the evoked overflow of tritium when preparations were stimulated with conditions that led to marked alpha(2)-a utoinhibition (120 pulses at 3 Hz), but not when stimulated with conditions that led to little alpha(2)-autoinhibition (20 pulses at 50 Hz). 3 Blockade of alpha-adrenoceptors by phentolamine (1 or 10 mu M) reduced or abolished the effect of angiotensin II and bradykinin on the overflow resp onse to 120 pulses at 3 Hz. 4 Addition of the delta-opioid agonist [D-Ser(2)]-leucine enkephalin-Thr (D SLET, 0.1 mu M), or of neuropeptide Y (0.1 mu M), together with phentolamin e, restored the effect of angiotensin II and bradykinin. 5 The beta-adrenoceptor agonist terbutaline (10(-9)-10(-4) M) enhanced the evoked overflow of tritium irrespective of the degree of autoinhibition. 6 The experiments show that (i) a marked prejunctional facilitatory effect of angiotensin and bradykinin in mouse isolated atria requires prejunctiona l alpha(2)-autoinhibition; (ii) in the absence of alpha(2)-autoinhibition, activation of other prejunctional G(i/o) protein-coupled receptors, namely opioid and neuropeptide Y receptors, restores a marked effect of angiotensi n II and bradykinin; and (iii) the facilitatory effect of terbutaline is no t dependent upon the degree of alpha(2)-autoinhibition. The findings indica te that the major part of the release-enhancing effect elicited through pre junctional G(q/11) protein-coupled receptors is due to disruption of an ong oing, alpha(2)-autoreceptor-triggered G(i/o) protein mediated inhibition.