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 including those of neuronal and neuroendocrine origin. We report here that Cl(-)-channel antagonists of the niflumic acid-, but not stilbene disulphonic acid-class, produced a concentration-dependent inhibition of histamine-stimulated PLC activity in bovine adrenal medullary chromaffin cells. Low extracellular [Cl-] (10 mM) produced a similar degree of inhibition. While the mechanism(s) responsible for this inhibition are not resolved it may be significant that low extracellular Cl- also reduced the magnitude of the histamine-induced Ca2+ signal. Thus, PLC inhibition may be secondary to a reduction in Ca2+-inflow, a conclusion consistent with the known actions of niflumic acid-type compounds and the previously reported importance of Ca2+-influx in supporting histamine-stimulated PLC activity.
Roberts-Thomson
E L
EL
The Neuroscience Group, Faculty of Medicine and Health Sciences, University of Newcastle, Callaghan, New South Wales, Australia.
Palmer
S M
SM
Powis
D A
DA
Bunn
S J
SJ
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D018118:Chloride Channels / Q000187:drug effects* / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D005942:Gluconates / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects*; D009544:Niflumic Acid / Q000494:pharmacology; D009566:Nitrates / Q000494:pharmacology; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D013431:Sulfates / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*
D018118:Chloride Channels; D002712:Chlorides; D005942:Gluconates; D009566:Nitrates; D013431:Sulfates; C012036:sodium sulfate; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D009544:Niflumic Acid; D006632:Histamine; C031618:sodium nitrate; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; C030691:gluconic acid; D002118:Calcium