Molecular mechanism of cGMP-mediated smooth muscle relaxation

2000/01/01 by Jorge A. Carvajal, Jorge Carvajal C, Alfredo M. Germain +4 · 28 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Phosphodiesterase function and regulation #Nitric Oxide and Endothelin Effects #Ion channel regulation and function

paper · doi:10.1002/1097-4652(200009)184:3<409::aid-jcp16>3.0.co;2-k

Abstract

Contraction and relaxation of smooth muscle is a tightly regulated process involving numerous endogenous substances and their intracellular second messengers. We examine the key role of cyclic guanosine monophosphate (cGMP) in mediating smooth muscle relaxation. We briefly review the current art regarding cGMP generation and degradation, while focusing on the recent identification of the molecular mechanisms underlying cGMP-mediated smooth muscle relaxation. cGMP-induced SM relaxation is mediated mainly by cGMP-dependent protein kinase activation. It involves several molecular events culminating in a reduction in intracellular Ca(2+) concentration and a decrease in the sensitivity of the contractile system to Ca(2+). We propose that the cGMP-induced decrease in Ca(2+) sensitivity is a strategic way to achieve "active relaxation" of the smooth muscle. In summary, we present compelling evidence supporting a key role for cGMP as a mediator of smooth muscle relaxation in physiological and pharmacological settings.

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