Abstract
The putative calcium channel antagonist verapamil has been shown to affect a variety of other ion channels as well as neurotransmitter receptors. We report that verapamil reversibly inhibits binding of the nicotinic receptor probe 125I-α-bungarotoxin to membranes from rat brain, Torpedo californica, the rat pheochromocytoma cell line PC12 and the human medulloblastoma cell line TE671, with Ki values of 24.0, 90.5, 165.4 and 869.6 μM, respectively. These effects are calcium independent and insensitive to a variety of organic and inorganic calcium channel antagonists. While Hill coefficients suggest mechanistic differences for verapamil action in the tissues examined, derivative graphical analysis demonstrates a common mechanism of heterotypic, allosteric inhibition. Verapamil may be useful as a probe to elucidate aspects of receptor-effector coupling.
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