Histamine-stimulated phospholipase C activity in bovine adrenal medullary chromaffin cells: the effect of chloride-channel antagonists and low extracellular chloride concentrations

Histamine activates phospholipase C (PLC) in a number of cell-types includi ng those of neuronal and neuroendocrine origin. We report here that Cl--cha nnel antagonists of the niflumic acid-, but not stilbene disulphonic acid-c lass, produced a concentration-dependent inhibition of histamine-stimulated PLC activity in bovine adrenal medullary chromaffin cells. Low extracellul ar [Cl-] (10 mM) produced a similar degree of inhibition. While the mechani sm(s) responsible for this inhibition are not resolved it may be significan t that low extracellular Cl- also reduced the magnitude of the histamine-in duced Ca2+ signal. Thus, PLC inhibition may be secondary to a reduction in Ca2+-inflow, a conclusion consistent with the known actions of niflumic aci d-type compounds and the previously reported importance of Ca2+ influx in s upporting histamine-stimulated PLC activity. (C) 2000 Elsevier Science Irel and Ltd. All rights reserved.