Phospholipase C-mediated signalling is not required for histamine-induced catecholamine secretion from bovine chromaffin cells

被引:7
作者
Donald, AN [1 ]
Wallace, DJ [1 ]
McKenzie, S [1 ]
Marley, PD [1 ]
机构
[1] Univ Melbourne, Dept Pharmacol, Melbourne, Vic 3010, Australia
关键词
catecholamine secretion; chromaffin cells; histamine; inositol 1,4,5-trisphosphate; intracellular Ca2+ stores; phospholipase C;
D O I
10.1046/j.1471-4159.2002.00915.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A possible role for signalling through phospholipase C in histamine-induced catecholamine secretion from bovine adrenal chromaffin cells has been investigated. Secretion evoked by histamine over 10 min was not prevented by inhibiting inositol-1,4,5-trisphosphate receptors with 2-APB, by blocking ryanodine receptors with a combination of ryanodine and caffeine, or by depleting intracellular Ca2+ stores by pretreatment with thapsigargin. Inhibition of protein kinase C with Ro31-8220 also failed to reduce secretion. Inhibition of phospholipase C with ET-18-OCH3 reduced both histamine- and K+ -induced inositol phosphate responses by 70-80% without reducing their secretory responses. Stimulating phospholipase C with Pasteurella multocida toxin did not evoke secretion or enhance the secretory response to histamine. The secretory response to histamine was little affected by tetrodotoxin or by substituting extracellular Na+ with N -methyl-d-glucamine(+) or choline(+) , or by substituting external Cl- with nitrate(-) . Blocking various K+ channels with apamin, charybdotoxin, Ba2+ , tetraethylammonium, 4-aminopyridine, tertiapin or glibenclamide failed to reduce the ability of histamine to evoke secretion. These results indicate that histamine evokes secretion by a mechanism that does not require inositol-1,4,5-trisphosphate-mediated mobilization of stored Ca2+ , diacylglycerol-mediated activation of protein kinase C, or activation of phospholipase C. The results are consistent with histamine acting by depolarizing chromaffin cells through a phospholipase C-independent mechanism.
引用
收藏
页码:1116 / 1129
页数:14
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