Effect of modulators of tyrosine kinase activity on agonist-induced contraction in the rat pulmonary vascular smooth muscle.
In the rat isolated main pulmonary artery, we investigated the effect of a tyrosine kinase inhibitor (genistein) and that of a tyrosine phosphatase inhibitor (phenylarsine oxide) on agonist-induced contraction. Genistein (10 microM) reduced the amplitude of the contraction evoked by noradrenaline (0.1-10 microM) or angiotensin II (1-100 nM). Phenylarsine oxide (0.5 microM) increased the amplitude of the contraction evoked by these agonists. The effects of genistein and phenylarsine oxide on agonist-induced contractions were also observed in the presence of verapamil (10 microM). Thapsigargin (0.5 microM) increased the amplitude of the contraction induced by noradrenaline (1-10 microM) or angiotensin II (10-100 nM). Subsequent addition of genistein counteracted the effect of thapsigargin on noradrenaline- and angiotensin II-induced contraction. Dantrolene alone (100 microM) reduced noradrenaline- and angiotensin II- but not KCI-induced contraction. In the presence of dantrolene, genistein and phenylarsine oxide failed to modify noradrenaline- and angiotensin II-induced contraction. Finally, in beta-escin skinned preparations, genistein (10-20 microM) and phenylarsine oxide (0.5-1 microM) did not alter Ca(2+)-induced contraction. These results suggest that a tyrosine kinase activity is involved in the vasoconstrictor action of noradrenaline and angiotensin II in the pulmonary circulation. The stimulation of the tyrosine kinase activity appears to be linked to the depletion of an intracellular Ca2+ store.
Savineau
J P
JP
Laboratoire de Physiologie Cellulaire Respiratoire, Université Bordeaux 2, France.
Gonzalez De La Fuente
P
P
Marthan
R
R
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003620:Dantrolene / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004928:Escin / Q000494:pharmacology; D019833:Genistein; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000187:drug effects* / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D001152:Arsenicals; D004791:Enzyme Inhibitors; D007529:Isoflavones; D014662:Vasoconstrictor Agents; C029341:oxophenylarsine; D000804:Angiotensin II; D019284:Thapsigargin; D004928:Escin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D003620:Dantrolene; D002118:Calcium; D009638:Norepinephrine