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.