Histamine-induced calcium release and phorbol antagonism in cultured airway smooth muscle cells

Primary cultures of airway smooth muscle cells were exposed to histamine, and intracellular free calcium transients were measured by the calcium-sensitive dye fura-2. Stimulation with 100 microM histamine resulted in a rise in intracellular calcium from an unstimulated level of 178 +/- 25 to 497 +/- 154 nM Ca2+ (SE; n = 14) and a return to base-line free calcium concentration within 1 min of stimulation. Pretreatment of cells with the H1 receptor blocker pyrilamine (2.5 microM) abolished the response; however, the calcium transient was not altered by pretreatment with the H2 blocker cimetidine (50 microM), by chelation of external calcium, or by pretreatment with 2 mM Co2+ or 5 microM nifedipine. Activation of protein kinase c by 200 nM phorbol 12-myristate 13-acetate (PMA) resulted in no detectable rise in cytosolic calcium but completely blocked the release of internal calcium by histamine. We conclude that 1) histamine causes a transient rise of cytosolic calcium in airway smooth muscle, 2) the rise in cytosolic calcium is mediated by H1 receptor coupling that triggers release of internal calcium stores, and 3) activation of protein kinase c blocks the histamine-induced release of intracellular calcium.