PMID: 6409148Jul 27, 1983Paper

Synergistic inhibition of human platelet adenylate cyclase by stable GTP analogs and epinephrine

Biochimica Et Biophysica Acta
K H Jakobs, K Aktories

Abstract

Adenylate cyclase inhibition by stable GTP analogs and their interaction with epinephrine were studied in human platelet membranes. Whereas basal enzyme activity was increased by these nucleotides, the stable GTP analogs decreased the adenylate cyclase activity stimulated by fluoride or forskolin by maximally 60 to 70%, with the potency order, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) greater than guanyl-5'-ylimidodiphosphate greater than guanyl-5'-ylmethylenediphosphate. The inhibition of the forskolin-stimulated enzyme by GTP gamma S was half-maximal at about 4 nM, occurred after a time lag period, which was inversely related to the GTP gamma S concentration, and was resistant to washing of the membranes. Prostaglandin E1-stimulated activity exhibited a biphasic response towards GTP gamma S, with activation occurring at low (1 nM) and inhibition at higher GTP gamma S concentrations. The inhibitory effect of GTP gamma S was competitively antagonized by GTP. This antagonism was prevented by epinephrine, which inhibited the stimulated platelet adenylate cyclase in the presence of GTP to the same degree as observed with GTP gamma S alone. In the absence of GTP, epinephrine largely diminished the time lag required for the ...Continue Reading

References

May 5, 1978·Naunyn-Schmiedeberg's Archives of Pharmacology·K H JakobsG Schultz
Sep 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·D Cassel, Z Selinger
Sep 20, 1979·Biochimica Et Biophysica Acta·B S Tsai, R J Lefkowitz
Jan 1, 1978·FEBS Letters·K H JakobsG Schultz
Jan 1, 1980·Annual Review of Biochemistry·E M Ross, A G Gilman
May 29, 1981·Biochemical and Biophysical Research Communications·B B HoffmanR J Lefkowitz
Sep 30, 1982·Biochemical and Biophysical Research Communications·N FerryJ Hanoune

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Citations

Sep 1, 1987·Pflügers Archiv : European journal of physiology·J HeschelerW Trautwein
Aug 15, 1989·Biochemical and Biophysical Research Communications·J F Coquil, G Brunelle
Dec 3, 1984·European Journal of Biochemistry·K Aktories, K H Jakobs

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