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 angiotensin (AT(1)) and bradykinin (B(2)) was studied in mouse isolated atria. The preparations were labelled with [(3)H]-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)-autoinhibition (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 microM) reduced or abolished the effect of angiotensin II and bradykinin on the overflow response to 120 pulses at 3 Hz. 4. Addition of the delta-opioid agonist [D-Ser(2)]-leucine enkephalin-Thr (DSLET, 0.1 microM), or of neuropeptide Y (0.1 microM), together with phentolamine, 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 prejunctional 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 angiotensin II and bradykinin; and (iii) the facilitatory effect of terbutaline is not dependent upon the degree of alpha(2)-autoinhibition. The findings indicate that the major part of the release-enhancing effect elicited through prejunctional G(q/11) protein-coupled receptors is due to disruption of an ongoing, alpha(2)-autoreceptor-triggered G(i/o) protein mediated inhibition.