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 Citations (Scopus)

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

Fingerprint

Inositol Phosphates
Endothelins
Cyclic GMP
Endothelin-1
Pulmonary Artery
1-Methyl-3-isobutylxanthine
Phosphodiesterase Inhibitors
Baths
Tissue
Vasoconstrictor Agents
Colforsin
Phosphatidylinositols
Vascular Smooth Muscle
Cyclic AMP
Muscle
Hydrolysis

Keywords

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

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pharmacology

Cite this

cGMP inhibition of endothelin-stimulated inositol phosphate production in the fetal lamb pulmonary artery. / Millard, S. L.; Russell, J. A.; Morin, F. C.; Adolf, M. A.; Gugino, S. F.; Steinhorn, Robin H.

In: Pulmonary Pharmacology and Therapeutics, Vol. 11, No. 2-3, 04.1998, p. 201-204.

Research output: Contribution to journalArticle

Millard, S. L. ; Russell, J. A. ; Morin, F. C. ; Adolf, M. A. ; Gugino, S. F. ; Steinhorn, Robin H. / cGMP inhibition of endothelin-stimulated inositol phosphate production in the fetal lamb pulmonary artery. In: Pulmonary Pharmacology and Therapeutics. 1998 ; Vol. 11, No. 2-3. pp. 201-204.
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