cGMP inhibition of endothelin-stimulated inositol phosphate production in the fetal lamb pulmonary artery

S. L. Millard, J. A. Russell, F. C. Morin, M. A. Adolf, S. F. Gugino, Robin H Steinhorn

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Endothelin-1 (ET-1) stimulates inositol phosphate production in vascular smooth muscle. In the present study, interactions between cyclic GMP (cGMP), cyclic AMP (cAMP) and ET-1 in fetal lamb pulmonary arteries were investigated using phosphoinositide hydrolysis studies and tissue bath techniques. ET-1 was found to be a potent vasoconstrictor of these vessels, with an EC50 Of 15.8 nM. ET-1 stimulated total inositol phosphate (IP) production; basal IP production was 68 cpm/mg vs. 247 cm/mg with 1 μM ET-1. 8-bromo-cGMP (2 mM) significantly increased the threshold of ET-1 concentration for pulmonary artery contraction, but had no effect on IP production. Zaprinast (a selective type V phosphodiesterase inhibitor, 60 μM) did not affect ET-l-induced contractility or LP production. IBMX (0.5 mM), a non-specific phosphodiesterase inhibitor, inhibited the potent and maximal effects of ET-1 in arterial contraction and decreased ET-1-stimulated IP production by 49%, while forskolin had a lesser effect in the tissue bath and no effect on IP production. Thus, 8-bromo-cGMP and IBMX alter the contractile effects of ET-1 in the fetal pulmonary artery and IBMX also inhibits inositol phosphate production. The cross-talk mechanisms of these agents require further investigation.

Original languageEnglish (US)
Pages (from-to)201-204
Number of pages4
JournalPulmonary Pharmacology and Therapeutics
Volume11
Issue number2-3
DOIs
StatePublished - Apr 1998
Externally publishedYes

Keywords

  • Cyclic GMP
  • Endothelin
  • Ovine
  • Phosphodiesterase
  • Phosphoinositide hydrolysis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pharmacology

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    Millard, S. L., Russell, J. A., Morin, F. C., Adolf, M. A., Gugino, S. F., & Steinhorn, R. H. (1998). cGMP inhibition of endothelin-stimulated inositol phosphate production in the fetal lamb pulmonary artery. Pulmonary Pharmacology and Therapeutics, 11(2-3), 201-204. https://doi.org/10.1006/pupt.1998.0138