Cytochrome P-450 may link intracellular Ca2+ stores with plasma membrane Ca2+ influx - PubMed (original) (raw)

J Alvarez et al. Biochem J. 1991.

Abstract

We have studied the mechanism of the regulation of plasma membrane Ca2+ permeability by the degree of filling of the intracellular Ca2+ stores. Using Mn2+ as a Ca2+ surrogate for plasma membrane Ca2+ channels, we found that Mn2+ uptake by rat thymocytes is inversely related to the degree of filling of the intracellular Ca2+ stores. This store-dependent plasma membrane permeability is inhibited by oxygen scavenging, CO, imidazole antimycotics and other cytochrome P-450 inhibitors. The pattern of inhibition is similar to that reported previously for the inhibition of microsomal cytochrome P-450-mediated aryl hydrocarbon hydroxylase activity of lymphocytes. Several calmodulin antagonists, both phenothiazinic (trifluoperazine, fluphenazine and chlorpromazine) and dibenzodiazepinic (clozapine), accelerate Mn2+ uptake by cells with Ca2(+)-filled stores, and this effect is prevented by imidazole antimycotics. Our results suggest that cytochrome P-450 may be the link between the stores and the plasma membrane Ca2+ pathway. We propose a model in which this cytochrome, sited at the stores, stimulates plasma membrane Ca2+ influx. This stimulatory effect is, in turn, prevented by the presence of Ca2+ inside the stores, possibly via a calmodulin-dependent mechanism.

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References

    1. Annu Rev Physiol. 1989;51:107-24 - PubMed
    1. Biochem J. 1990 Oct 15;271(2):535-40 - PubMed
    1. Biochem Biophys Res Commun. 1989 Jul 14;162(1):24-9 - PubMed
    1. Biochem J. 1990 Feb 1;265(3):675-80 - PubMed
    1. Biochem J. 1990 Feb 1;265(3):915-8 - PubMed

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