Inhibition of EGF-induced vasoconstriction in isolated rabbit aortic rings with the tyrosine kinase inhibitor RG50864.
The tyrosine kinase inhibitor RG50864 attenuated EGF-induced tension development dose-dependently. Similarly, contractions to a phorbolester were affected by 10 microM RG50864. In comparison, vasoconstrictor activities of norepinephrine, endothelin and Bay K 8644 remained unaltered. Western blots using antiphosphotyrosine antibodies, revealed a time-dependent increase in EGF-induced EGF-receptor autophosphorylation as well as tyrosine phosphorylation of a 55 kDalton cytosolic protein. While the extent of EGF-receptor autophosphorylation remained unaltered in the presence of 10 microM RG50864, phosphorylation of the 55 kD band was decreased two-fold. In summary, in rabbit aorta RG50864 is an inhibitor of EGF-induced vasoconstriction; this inhibitory effect does not appear to be mediated through inhibition of EGF-receptor autophosphorylation but may involve a 55 kD cytosolic protein substrate.
Merkel
L A
LA
Rhône-Poulenc Rorer Central Research.
Rivera
L M
LM
Colussi
D J
DJ
Perrone
M H
MH
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000502:physiology*; D002396:Catechols / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011817:Rabbits; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D020032:Tyrphostins; D014661:Vasoconstriction / Q000187:drug effects*
D002396:Catechols; D009570:Nitriles; D010750:Phosphoproteins; D020032:Tyrphostins; C060152:tyrphostin 47; D019000:Phosphotyrosine; D015240:Phorbol 12,13-Dibutyrate; D014443:Tyrosine; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases