Pharmacological actions of the calcium antagonist propyl-methylenedioxyindene in skinned vascular smooth muscle

Author:

Wong Wai-Shiu,Rahwan Ralf G.

Abstract

Previous studies provided strong evidence that propyl-methylenedioxyindene (pr-MDI) interfered with calcium at an intracellular site. To further characterize the mechanism of action of pr-MDI, its pharmacological actions on chemically skinned vascular smooth muscle were examined. Rat caudal artery strips were chemically skinned with saponin (0.15 mg/mL for 1 h). The efficiency of the skinning was evidenced by a loss of contractile response to 74 mM K+. The intactness of the regulatory and contractile proteins was ascertained by the ability of the skinned tissue to contract in response to Ca2+ (free Ca2+ concentration of 10−4 or 10−6 M). Caffeine (25 mM) induced contraction was used as an index of the functional integrity of the sarcoplasmic reticulum in the skinned preparations. Contraction of the skinned artery with a free Ca2+ concentration of 10−6 M was significantly obtunded by 1 × 10−4 M trifluoperazine (a calmodulin antagonist) but not by 1 × 10−4 M pr-MDI. Contraction of the skinned artery evoked by 25 mM caffeine in the absence of extracellular calcium was significantly obtunded by 1 × 10−4 M pr-MDI but not by 1 × 10−6 M nifedipine (a calcium channel blocker). The results indicate that pr-MDI acts intracellularly to block calcium mobilization from the sarcoplasmic reticulum without directly interfering with the regulatory and contractile proteins.

Publisher

Canadian Science Publishing

Subject

Physiology (medical),Pharmacology,General Medicine,Physiology

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