Electrophysiologic and biochemical studies on the putative Ca++ channel blocker MDL 12,330A in an endocrine cell.
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(-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, MDL 12,330A 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 stimulated at 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.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers; D002460:Cell Line; D004553:Electric Conductivity; D007097:Imines / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D007097:Imines; D007473:Ion Channels; C014925:RMI 12330A; D002118:Calcium