MODULATORY EFFECT OF BRADYKININ ON THE RELEASE OF NORADRENALINE FROM RAT ISOLATED ATRIA

1 We investigated the modulation by bradykinin (BK) of electrically induced noradrenaline release in rat isolated atria preincubated with [H-3]-noradrenaline. 2 BK (1-100 nM) enhanced significantly the stimulation-induced outflow of radioactivity in a concentration-dependent manner with a calculated EC(50) of 0.58 nM. 3 Des-Arg(9)-BK (0.1-100 nM), a Selective B-1 receptor agonist, did not modify the stimulation-induced outflow of radioactivity. Hoe 140 (10 nM), a selective B-2 receptor antagonist, but not [Leu(8)]-des-Arg(9)-BK (100 nM), a selective B-1 receptor antagonist, blocked the facilitatory effect of BK. 4 The effect of BK was not affected by diclofenac (1 mu M), a cyclo-oxygenase inhibitor. Bisindolylmaleimide (1 mu M), a protein kinase C inhibitor, significantly reduced the facilitatory effect of BK (10 nM), angiotensin II (0.3 mu M) and phorbol dibutyrate (0.1 and 1 mu M) but not of fenoterol (1 mu M). 5 The results suggest that BK enhances noradrenaline release via a prejunctional B-2 kinin receptor in the rat atrium. The effect appears to involve protein kinase C as a second messenger.