Abstract
The activity of the adenylate cyclase inhibitory guanine-nucleotide-binding regulatory protein (Gi), measured as inhibition of forskolin-stimulated cyclic AMP formation, and its regulation by various nucleotides and the inhibitory alpha 2-adrenoreceptor agonist epinephrine was studied in membranes of human platelets. When adenylate cyclase activity was measured with ATP as substrate and in the absence of a nucleoside-triphosphate-regenerating system, GTP (0.1-10 microM) by itself potently and efficiently inhibited the enzyme. GDP was almost as potent and as effective as GTP. In the additional presence of epinephrine, the potencies of both GTP and GDP were increased about threefold, while maximal inhibition by these nucleotides was only slightly increased by the receptor agonist. In contrast to GTP and GDP, the metabolically stable GDP analog, guanosine 5'-[beta-thio]diphosphate, had only a very small effect, suggesting that GDP but not its stable analog is converted to the active GTP. Addition of UDP (1 mM), used to block the GDP to GTP conversion reaction, completely suppressed the inhibitory effect of GDP, while that caused by GTP was not affected. Most important, the inhibitory receptor agonist epinephrine counteracted the s...Continue Reading
References
Mar 28, 1979·Biochimica Et Biophysica Acta·T F Walseth, R A Johnson
Nov 1, 1979·FEBS Letters·K AktoriesK H Jakobs
Nov 29, 1979·Nature·D M Cooper, M Rodbell
Jul 15, 1988·European Journal of Biochemistry·R SeifertK H Jakobs
Aug 30, 1985·Biochemical and Biophysical Research Communications·N Kimura, N Shimada
Jan 29, 1986·Biochemical and Biophysical Research Communications·N Kimura, N Shimada
Dec 15, 1986·Biochemical Pharmacology·S C Lam, M A Packham
Jan 1, 1986·Annual Review of Cell Biology·L Stryer, H R Bourne
Nov 16, 1987·FEBS Letters·P Gierschik, K H Jakobs
Aug 1, 1987·Kidney International·M M SchwartzE J Lewis
Apr 1, 1980·Thrombosis Research·K P Mellwig, K H Jakobs
Jul 27, 1983·Biochimica Et Biophysica Acta·K H Jakobs, K Aktories
Citations
Jan 4, 2007·Naunyn-Schmiedeberg's Archives of Pharmacology·Thomas Wieland
Sep 8, 2006·Journal of Bioenergetics and Biomembranes·Hans-Joerg Hippe, Thomas Wieland
Feb 9, 1996·Biochemical Pharmacology·J F KlinkerR Seifert
Feb 1, 1992·Trends in Pharmacological Sciences·M L Lacombe, K H Jakobs
Sep 12, 1991·European Journal of Pharmacology·T WielandK H Jakobs
Aug 24, 1999·European Journal of Pharmacology·D ZhangL Y Liu-Chen
Dec 17, 1990·Brain Research·R S JopeM B Williams
May 16, 2008·The Journal of Biological Chemistry·Magnus GrenegårdTomas L Lindahl
Dec 18, 2002·The Journal of Biological Chemistry·Friederike CuelloThomas Wieland
May 19, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Klaus AktoriesThomas Wieland
Jan 26, 2012·Platelets·Erik TournoijJan-Willem N Akkerman
Jun 1, 1990·Molecular and Cellular Biology·A N Hegde, M R Das