CHARACTERIZATION AND CA-2+ REQUIREMENT OF HISTAMINE-INDUCED CATECHOLAMINE SECRETION IN CULTURED BOVINE CHROMAFFIN CELLS

The stimulation of cultured bovine chromaffin cells with histamine induced a continuous catecholamine secretion (EC50 = 3 x 10(-7) M) via the H-1 receptor, in addition to an initial catecholamine burst due to a nonspecific stimulatory effect at higher doses (greater-than-or-equal-to 10(-4) M). The continuous secretion showed little desensitization and lasted for more than 1 h. In fura-2-loaded cells, the stimulation with histamine evoked a transient rise of intracellular free Ca2+ concentration ([Ca2+]i) which lasted only for a few minutes and was followed by a sustained [Ca2+]i rise which continued for more than 20 min. The addition of an activator for the L-type voltage-sensitive Ca2+ channel, i.e., Bay K 8644 (1-mu-M), facilitated the sustained [Ca2+]i rise, as well as the secretion, whereas the addition of relatively high concentrations of Ca2+-channel blockers (10-mu-M) suppressed the sustained [Ca2+]i rise and part of the secretion. Removal of extracellular Ca2+ completely abolished continuous secretion and sustained [Ca2+]i rise. When the external Ca2+ level was elevated, both sustained [Ca2+]i rise and continuous secretion were enhanced in a similar Ca2+-dependent manner, showing saturation with around 1-3 mM Ca2+. This Ca2+ dependence was clearly different from that observed with high K+ and nicotine, which is mediated by the L-type Ca2+ channel, in which the responses showed little or no saturation when the Ca2+ level was increased. The results indicate that stimulation with histamine induces a continuous secretion via the H-1 receptor, in addition to a transient and nonspecific secretion at higher doses. At least part of the continuous secretion is induced by a sustained [Ca2+]i rise due to the continuous Ca2+ influx through Ca2+ channels. These channels are sensitive to dihydropyridines, but do not appear to be identical to the L-type voltage-sensitive Ca2+ channel.