A kinetic analysis of activation of smooth muscle adenylate cyclase by forskolin

Archives of Biochemistry and Biophysics
J F Krall

Abstract

Forskolin action was studied using uterine smooth muscle adenylate cyclase, an enzyme form that is slowly and irreversibly activated by treatment with nonhydrolyzable GTP analogs. Activation of the particulate smooth muscle enzyme by prolonged treatment with Gpp[NH]p (guanyl-5'-yl imidodiphosphate) at 24 degrees C followed simple Michaelis-Menten kinetics with respect to the guanine nucleotide. Under these treatment conditions, forskolin increased both the Vmax and the Km for Gpp[NH]p, suggesting diterpene action affected the guanine nucleotide-binding coupling factor. Sensitivity of a detergent-solubilized form of the enzyme to stimulation by both Gpp[NH]p and forskolin was much more labile at 4 degrees C than was the Mn+2 sensitivity of the catalytic subunit. In the particulate form, the catalytic subunit was more resistant to the denaturing effects of N-ethylmaleimide than was its sensitivity to stimulation by Gpp[NH]p or forskolin. Forskolin stimulation of the particulate form of the enzyme followed simple Michaelis-Menten kinetics with respect to the concentration of the diterpene. Denaturation of the enzyme by treatment with N-ethylmaleimide lowered the Vmax and increased the Km for forskolin, further suggesting that fors...Continue Reading

References

Jun 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·K B SeamonJ W Daly
Feb 1, 1982·Archives of Biochemistry and Biophysics·J F Krall, S G Korenman

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