Mechanism of cyclic GMP inhibition of inositol phosphate formation in rat aorta segments and cultured bovine aortic smooth muscle cells

Masato Hirata, K. P. Kohse, C. H. Chang, T. Ikebe, F. Murad

Research output: Contribution to journalArticle

171 Citations (Scopus)

Abstract

In order to clarify the mechanism(s) by which cyclic GMP inhibits the generation of inositol phosphates in rat aorta segments and cultured bovine aortic smooth muscle cells, we studied phosphoinositide hydrolysis and GTPase activity in homogenates and membrane preparations of cultured bovine aortic smooth muscle cells. Pretreatment of homogenate preparations with cyclic GMP plus ATP did not inhibit [8-arginine, 3 H] vasopressin (AVP) binding, but resulted in a total suppression of the AVP-induced GTPase activation. The pretreatment with cyclic GMP and ATP also inhibited the formation of inositol phosphates induced by AVP in the presence of low concentrations of guanosine 5'-(γ-thio)triphosphate (GTPγS), or by high concentrations of GTPγS alone. However, the formation of inositol phosphates by high concentrations of Ca 2+ alone was not blocked. These results suggest that the ability of cyclic GMP to inhibit phosphoinositide hydrolysis results from a inhibition of a guanine nucleotide regulatory protein activation, and the interaction between guanine nucleotide regulatory protein and phospholipase C. While the precise site of this inhibition is not presently known, the inhibition by cyclic GMP is dependent upon the addition of ATP and probably entails a phosphorylation event since adenylylimidodiphosphate can not substitute for the ATP requirement.

Original languageEnglish
Pages (from-to)1268-1273
Number of pages6
JournalJournal of Biological Chemistry
Volume265
Issue number3
Publication statusPublished - Feb 15 1990

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Inositol Phosphates
Cyclic GMP
Smooth Muscle Myocytes
Muscle
Aorta
Rats
Cells
Adenosine Triphosphate
Vasopressins
Arginine
GTP Phosphohydrolases
Phosphatidylinositols
GTP-Binding Proteins
Hydrolysis
Chemical activation
Adenylyl Imidodiphosphate
Phosphorylation
Guanosine
Type C Phospholipases
Protein C

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Mechanism of cyclic GMP inhibition of inositol phosphate formation in rat aorta segments and cultured bovine aortic smooth muscle cells. / Hirata, Masato; Kohse, K. P.; Chang, C. H.; Ikebe, T.; Murad, F.

In: Journal of Biological Chemistry, Vol. 265, No. 3, 15.02.1990, p. 1268-1273.

Research output: Contribution to journalArticle

Hirata, Masato ; Kohse, K. P. ; Chang, C. H. ; Ikebe, T. ; Murad, F. / Mechanism of cyclic GMP inhibition of inositol phosphate formation in rat aorta segments and cultured bovine aortic smooth muscle cells. In: Journal of Biological Chemistry. 1990 ; Vol. 265, No. 3. pp. 1268-1273.
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