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Electrophysiologic and biochemical studies on the putative calcium channel blocker mdl 12330a in an endocrine cell


, : Electrophysiologic and biochemical studies on the putative calcium channel blocker mdl 12330a in an endocrine cell. Journal of Pharmacology & Experimental Therapeutics 243(1): 402-407

MDL 12,330A is a molecule structurally unrelated to other organic Ca++ channel ligands that may alter Ca++ channel function. Using whole cell patch clamp, [3H]PN200-110 binding and 45Ca++ uptake studies, we examined the effects of this compound on voltage-dependent Ca++ channels in rat anterior pituitary cells. At a concentration of 10-5Ca++ uptake studies, we examined the effects of this compound on voltage-dependent Ca++ channels in rat anterior pituitary cells. At a concentration of 10-5 M, MDL 12,330A showed little effect on outward K+ current, Na+ current or low-threshold Ca++ current in this cell line. At 10-6 M, MDL12, 330A reversibly inhibited slow Ca++ current in a voltage-dependent manner. 45Ca++ uptake was also blocked by this compound at 10-6 M, whereas [3H]PN200-110 binding was stimulant concentrations of 10-7 to 10-6 M. The results are consistent with an interaction of MDL 12,330A with slow Ca++ channels at a site allosterically linked to the 1,4-dihydropyridine binding site.

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