Effects of SQ 31,765, a new calcium channel blocker, on stress and myosin light chain phosphorylation in swine carotid media.
The vasorelaxant activity of SQ 31,765 and diltiazem was studied in intact and Triton X-100 detergent-skinned fibers of the swine carotid media. Both calcium channel blockers were used to relax or prevent contractions induced by depolarization with 110 mM KCl. The potencies of SQ 31,765 and diltiazem were similar for relaxing or preventing the tonic component of KCl-induced contractions of intact vascular smooth muscle strips. A significantly higher concentration of either compound was required to prevent the phasic component of the contraction. The possible direct effects of these calcium channel blockers on contractile function were examined in the detergent-skinned carotid medial fiber contracted with 3 microM Ca2+. Both stress and myosin light chain (MLC) phosphorylation levels were determined in detergent-skinned fibers in the presence and absence of the channel blockers. Neither compound affected stress or MLC phosphorylation in Ca2(+)-contracted detergent-skinned fibers, indicating a lack of direct effect on the contractile proteins. Thus, SQ 31,765 appears to act selectively at the level of the sarcolemma.
Moreland
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Bristol-Myers Squibb Pharmaceutical Research Institute, Department of Pharmacology, Princeton, New Jersey 08543.
McMullen
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D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects; D003285:Contractile Proteins / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009218:Myosins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D013314:Stress, Mechanical; D013552:Swine
D001552:Benzazepines; D002121:Calcium Channel Blockers; D003285:Contractile Proteins; C062147:SQ 31765; D009218:Myosins; D004110:Diltiazem