Abstract
1. A pharmacological characterization of tyrosine kinase inhibitors (TKI) belonging to two distinct groups (competitors at the ATP-binding site and the substrate-binding site, respectively) was performed, based on their effects on the contractility of rat mesenteric arteries. 2. Both the ATP-site competitors (genistein and its inactive analogue, daidzein) and the substrate-site competitors (tyrphostins A-23, A-47 and the inactive analogue, A-1) reversibly inhibited noradrenaline (NA, (10 microM)) and KCl (125 mM) induced contractions, concentration-dependently. Genistein was slightly but significantly more potent than daidzein; the tyrphostins were all less potent than genistein, and there were no significant differences between the individual potencies. The tyrosine kinase substrate-site inhibitor bis-tyrphostin had no inhibitory effect. 3. Genistein, daidzein, A-23 and A-47 each suppressed the contraction induced by Ca2+ (1 microM) in alpha-toxin permeabilized arteries. A-1 and bis-tyrphostin had little or no effect on contraction of the permeabilized arteries. 4. Genistein was significantly more potent than daidzein with respect to inhibition of the contraction induced by 200 nM Ca2+ in the presence of NA (100 microM) and GTP (3 microM). The effect of A-23, A-47, A-1 and bis-tyrphostin was similar in permeabilized arteries activated with Ca2+ (200 nM) + NA (100 microM) + GTP (3 microM) and permeabilized arteries activated with 1 microM Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Akiyama T., Ishida J., Nakagawa S., Ogawara H., Watanabe S., Itoh N., Shibuya M., Fukami Y. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem. 1987 Apr 25;262(12):5592–5595. [PubMed] [Google Scholar]
- Aprigliano O., Hermsmeyer K. In vitro denervation of the portal vein and caudal artery of the rat. J Pharmacol Exp Ther. 1976 Sep;198(3):568–577. [PubMed] [Google Scholar]
- Auger K. R., Serunian L. A., Soltoff S. P., Libby P., Cantley L. C. PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells. Cell. 1989 Apr 7;57(1):167–175. doi: 10.1016/0092-8674(89)90182-7. [DOI] [PubMed] [Google Scholar]
- Bishop J. M. The molecular genetics of cancer. Science. 1987 Jan 16;235(4786):305–311. doi: 10.1126/science.3541204. [DOI] [PubMed] [Google Scholar]
- Casnellie J. E. Protein kinase inhibitors: probes for the functions of protein phosphorylation. Adv Pharmacol. 1991;22:167–205. doi: 10.1016/s1054-3589(08)60035-6. [DOI] [PubMed] [Google Scholar]
- Di Salvo J., Steusloff A., Semenchuk L., Satoh S., Kolquist K., Pfitzer G. Tyrosine kinase inhibitors suppress agonist-induced contraction in smooth muscle. Biochem Biophys Res Commun. 1993 Feb 15;190(3):968–974. doi: 10.1006/bbrc.1993.1144. [DOI] [PubMed] [Google Scholar]
- Draetta G., Piwnica-Worms H., Morrison D., Druker B., Roberts T., Beach D. Human cdc2 protein kinase is a major cell-cycle regulated tyrosine kinase substrate. Nature. 1988 Dec 22;336(6201):738–744. doi: 10.1038/336738a0. [DOI] [PubMed] [Google Scholar]
- Glenney J. R., Jr Tyrosine-phosphorylated proteins: mediators of signal transduction from the tyrosine kinases. Biochim Biophys Acta. 1992 Mar 16;1134(2):113–127. doi: 10.1016/0167-4889(92)90034-9. [DOI] [PubMed] [Google Scholar]
- Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
- Hollenberg M. D. Tyrosine kinase pathways and the regulation of smooth muscle contractility. Trends Pharmacol Sci. 1994 Apr;15(4):108–114. doi: 10.1016/0165-6147(94)90046-9. [DOI] [PubMed] [Google Scholar]
- Jensen P. E., Mulvany M. J., Aalkjaer C. Endogenous and exogenous agonist-induced changes in the coupling between [Ca2+]i and force in rat resistance arteries. Pflugers Arch. 1992 Apr;420(5-6):536–543. doi: 10.1007/BF00374630. [DOI] [PubMed] [Google Scholar]
- Jensen P. E., Mulvany M. J., Aalkjaer C., Nilsson H., Yamaguchi H. Free cytosolic Ca2+ measured with Ca(2+)-selective electrodes and fura 2 in rat mesenteric resistance arteries. Am J Physiol. 1993 Aug;265(2 Pt 2):H741–H746. doi: 10.1152/ajpheart.1993.265.2.H741. [DOI] [PubMed] [Google Scholar]
- Levitzki A., Gilon C. Tyrphostins as molecular tools and potential antiproliferative drugs. Trends Pharmacol Sci. 1991 May;12(5):171–174. doi: 10.1016/0165-6147(91)90538-4. [DOI] [PubMed] [Google Scholar]
- Lyall R. M., Zilberstein A., Gazit A., Gilon C., Levitzki A., Schlessinger J. Tyrphostins inhibit epidermal growth factor (EGF)-receptor tyrosine kinase activity in living cells and EGF-stimulated cell proliferation. J Biol Chem. 1989 Aug 25;264(24):14503–14509. [PubMed] [Google Scholar]
- Merkel L. A., Rivera L. M., Colussi D. J., Perrone M. H. Inhibition of EGF-induced vasoconstriction in isolated rabbit aortic rings with the tyrosine kinase inhibitor RG50864. Biochem Biophys Res Commun. 1993 May 14;192(3):1319–1326. doi: 10.1006/bbrc.1993.1560. [DOI] [PubMed] [Google Scholar]
- Mulvany M. J., Halpern W. Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ Res. 1977 Jul;41(1):19–26. doi: 10.1161/01.res.41.1.19. [DOI] [PubMed] [Google Scholar]
- Nilsson H., Jensen P. E., Mulvany M. J. Minor role for direct adrenoceptor-mediated calcium entry in rat mesenteric small arteries. J Vasc Res. 1994 Nov-Dec;31(6):314–321. doi: 10.1159/000159059. [DOI] [PubMed] [Google Scholar]
- O'Dell T. J., Kandel E. R., Grant S. G. Long-term potentiation in the hippocampus is blocked by tyrosine kinase inhibitors. Nature. 1991 Oct 10;353(6344):558–560. doi: 10.1038/353558a0. [DOI] [PubMed] [Google Scholar]
- Sargeant P., Farndale R. W., Sage S. O. ADP- and thapsigargin-evoked Ca2+ entry and protein-tyrosine phosphorylation are inhibited by the tyrosine kinase inhibitors genistein and methyl-2,5-dihydroxycinnamate in fura-2-loaded human platelets. J Biol Chem. 1993 Aug 25;268(24):18151–18156. [PubMed] [Google Scholar]
- Sauro M. D., Thomas B. Tyrphostin attenuates platelet-derived growth factor-induced contraction in aortic smooth muscle through inhibition of protein tyrosine kinase(s). J Pharmacol Exp Ther. 1993 Dec;267(3):1119–1125. [PubMed] [Google Scholar]
- Schaller M. D., Parsons J. T. Focal adhesion kinase: an integrin-linked protein tyrosine kinase. Trends Cell Biol. 1993 Aug;3(8):258–262. doi: 10.1016/0962-8924(93)90053-4. [DOI] [PubMed] [Google Scholar]
- Tsuda T., Kawahara Y., Shii K., Koide M., Ishida Y., Yokoyama M. Vasoconstrictor-induced protein-tyrosine phosphorylation in cultured vascular smooth muscle cells. FEBS Lett. 1991 Jul 8;285(1):44–48. doi: 10.1016/0014-5793(91)80721-e. [DOI] [PubMed] [Google Scholar]
- Weiss R. H., Nuccitelli R. Inhibition of tyrosine phosphorylation prevents thrombin-induced mitogenesis, but not intracellular free calcium release, in vascular smooth muscle cells. J Biol Chem. 1992 Mar 15;267(8):5608–5613. [PubMed] [Google Scholar]
- Wijetunge S., Aalkjaer C., Schachter M., Hughes A. D. Tyrosine kinase inhibitors block calcium channel currents in vascular smooth muscle cells. Biochem Biophys Res Commun. 1992 Dec 30;189(3):1620–1623. doi: 10.1016/0006-291x(92)90262-j. [DOI] [PubMed] [Google Scholar]
- Yang S. G., Saifeddine M., Hollenberg M. D. Tyrosine kinase inhibitors and the contractile action of epidermal growth factor-urogastrone and other agonists in gastric smooth muscle. Can J Physiol Pharmacol. 1992 Jan;70(1):85–93. doi: 10.1139/y92-012. [DOI] [PubMed] [Google Scholar]
- Yang S. G., Saifeddine M., Laniyonu A., Hollenberg M. D. Distinct signal transduction pathways for angiotensin-II in guinea pig gastric smooth muscle: differential blockade by indomethacin and tyrosine kinase inhibitors. J Pharmacol Exp Ther. 1993 Feb;264(2):958–966. [PubMed] [Google Scholar]