GTP gamma S-dependent regulation of smooth muscle contractile elements.
Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) increases the sensitivity of the contractile response to activation by Ca2+ in permeabilized tracheal smooth muscle. Increased tension was associated with a proportional increase in myosin light chain phosphorylation. The site of phosphorylation was determined to be serine-19, which corresponds to the site rapidly phosphorylated by myosin light chain kinase. GTP gamma S did not affect the contraction induced by the protein phosphatase inhibitor okadaic acid but did enhance contraction produced by Ca(2+)-independent myosin light chain kinase. In tracheal homogenates Ca(2+)-dependent myosin light chain kinase activity was not affected by GTP gamma S; however, dephosphorylation of 32P-labeled heavy meromyosin by phosphatase was inhibited. Thus GTP gamma S may increase the Ca2+ sensitivity of contractile elements in tracheal smooth muscle by inhibition of protein phosphatase activity toward myosin light chain.
Kubota
Y
Y
Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235.
Nomura
M
M
Kamm
K E
KE
Mumby
M C
MC
Stull
J T
JT
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D004988:Ethers, Cyclic / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism*; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D012503:Saponins / Q000494:pharmacology
D004988:Ethers, Cyclic; D012503:Saponins; D019319:Okadaic Acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009219:Myosin-Light-Chain Kinase; D010749:Phosphoprotein Phosphatases; D009218:Myosins; D002118:Calcium