Selectivity of calcium antagonistic action in vascular smooth muscle.
Various mechanisms can account for selective inhibition by calcium influx blocking drugs of smooth muscle contractile activity. Diltiazem inhibits calcium influx activated by membrane depolarization as well as alpha adrenergic receptor stimulation. Diltiazem does not inhibit intracellular calcium release nor cause net calcium extrusion up to concentrations of 10(-5) M. As with other calcium influx blocking agents, diltiazem is a potent inhibitor for modes of activation that depend entirely on the presence of extracellular calcium. The calcium influx was found to be mediated by at least three different pathways: one activated by depolarization and highly sensitive to D-600, a second activated by norepinephrine and less sensitive to D-600, and a third "passive leak," that is insensitive to D-600 and accounts for calcium permeability in the resting state. Molecular differences among these various calcium channels may provide the basis for specificity of action of the calcium influx blocking agents.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003329:Coronary Vasospasm / Q000188:drug therapy / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007473:Ion Channels / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007473:Ion Channels; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine