Molecular mechanism of cGMP-mediated smooth muscle relaxation.
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.
Carvajal
J A
JA
Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Maryland-Baltimore, Baltimore, Maryland 21201, USA. jcarv001@umaryland.edu
Germain
A M
AM
Huidobro-Toro
J P
JP
Weiner
C P
CP
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D009126:Muscle Relaxation / Q000502:physiology*; D009130:Muscle, Smooth / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D015290:Second Messenger Systems
D007473:Ion Channels; D010455:Peptides; D009569:Nitric Oxide; D002248:Carbon Monoxide; D015544:Inositol 1,4,5-Trisphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D010727:Phosphoric Diester Hydrolases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D002118:Calcium