KININS MODULATE NORADRENALINE RELEASE FRO M PC12 CELLS VIA B(2)-RECEPTORS

In this study the direct effects of bradykinin and desArg9-bradykinin on noradrenaline release from rat pheochromocytoma cell line PC12 was investigated. Furthermore, the influence of inhibitors of angiotensin I converting enzyme (ACE) on the sensitivity to and the metabolism of kinins was tested in this model. Bradykinin proved to be a more potent stimulus (EC50 = 1 nM) compared to acetylcholine and released up to 5 0% of the total cellular noradrenaline content. This effect was inhibi ted competitively by the B2-antagonist HOE 890307 S (pA2 = 8,9), while the B2-antagonist Thi5,8, D-Phe7!-bradykinin had a weak agonistic ef fect. The B1-agonist desArg9-bradykinin exerted a stimulatory activity only in concentrations beyond 10 muM. Pretreatment of the cells with the ACE-inhibitor ramiprilat or with lipopolysaccharides did not influ ence the effects of bradykinin and desArg9-bradykinin. The extracellul ar degradation of bradykinin by PC12 cells was completely blocked by r amiprilat. The results demonstrate that PC12 cells are endowed with B2 -receptors, which directly stimulate noradrenaline secretion, and poss ess kininase II, which is mainly responsible for the extracellular deg radation of bradykinin.