AGONIST-INDUCED INHIBITION OF INOSITOL-TRISPHOSPHATE-ACTIVATED IK(CA) IN NG108-15 NEUROBLASTOMA HYBRID-CELLS
AGONIST-INDUCED INHIBITION OF INOSITOL-TRISPHOSPHATE-ACTIVATED IK(CA) IN NG108-15 NEUROBLASTOMA HYBRID-CELLS
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DOI：
10.1007/bf00374292
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发表时间：
1993-01-01
影响因子：
4.5
通讯作者：
ROBBINS, J
中科院分区：
文献类型：
--
作者：
ROBBINS, J
I(K(Ca)) activated by intracellular ionophoresis of inositol trisphosphate (IP3) or pressure-applied acetylcholine was inhibited by bradykinin and acetylcholine in NG108-15 cells transfected with ml receptors. The inhibition of the IP3-evoked current was complete at 10 muM acetylcholine. This inhibition was not seen if the current was evoked by intracellular ionophoresis of calcium ions. Only receptors the activate the phosphoinositide system in these cells produced this inhibition, i.e. transfected muscarinic ml and m3 and bradykinin receptors, but not muscarinic m2, m4 or adrenergic alpha2 receptors. This inhibition was not sensitive to pertussis toxin or staurosporine. The concentrations of acetylcholine needed to inhibit the evoked current were identical to those needed to raise intracellular calcium but tenfold less than those needed for the agonist to activate I(K(Ca)). In a normal calcium-containing superfusate, recovery from inhibition required around 8 min (half-time 4 min) after removal of acetylcholine. When the experiment was performed in calcium-free medium no recovery was seen after 8 min washing in drug-tree solution, but complete recovery was seen within 3 min (half-time 1.5 min) after adding calcium. Responses to repeated pressure applications of acetylcholine could be reversibly inhibited by acetylcholine and bradykinin. It seems, then. that there is no direct action of acetylcholine or bradykinin on the I(K(Ca)) channels themselves but that concentrations below those needed to activate I(K(Ca)) can empty and inhibit the IP3-sensitive calcium store. This may provide a mechanism for heterologous desensitization for phospholipase-C-linked receptor-mediated responses.
