Divalent cations effectively replace Ca2+ and support bradykinin induced noradrenaline release.

Bradykinin (BK), a nonapeptide acting at the B2-type BK-receptor, and depolarization with high KCl (50 mM), induce catecholamine secretion in pheochromocytoma cells (PC-12). The mechanism underlying the BK-induced release, which is absolutely Ca2(+)-dependent, is not yet understood. Alkaline metals, barium (Ba2+), strontium (Sr2+) and other metal cations, manganese (Mn2+) or lanthanum (La3+), support BK-induced [3H]noradrenaline ([3H]NA) release. The extent of supporting transmitter release is dependent upon the specificity of the extracellular cation, with rank order potency of: Ba2+ greater than Sr2+ greater than Ca2+ greater than Mn2+La3+. The same rank order potency was observed for supporting both BK- and K(+)-induced release. [3H]NA release in the presence of Ba2+ or Sr2+ was much greater than in the presence of Ca2+, and unlike with Ca2+ was not saturable at the highest concentration measured. La3+ and Mn2+ were significantly less effective than Ca2+ at supporting release. These results strongly suggest that extracellular Ca2+ entry is essential for release, and that BK mediates release via a receptor-operated Ca2+ channel.