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  • Title: Effects of inhibitors for tyrosine kinase and non-selective cation channel on capacitative Ca(2+) entry in rat ileal smooth muscle.
    Author: Ohta T, Yasuda W, Hasegawa A, Ito S, Nakazato Y.
    Journal: Eur J Pharmacol; 2000 Jan 10; 387(2):211-20. PubMed ID: 10650162.
    Abstract:
    The effects of tyrosine kinase inhibitors and non-selective cation channel blockers on capacitative Ca(2+) entry were examined in the presence of methoxyverapamil in rat ileal smooth muscles. In Ca(2+)-free solution, carbachol or caffeine produced a rapid contraction mediated by Ca(2+) release from the stores (Ca(2+)-release response), and then led to Ca(2+) depletion of the stores. Subsequently, reintroduction of Ca(2+) caused a transient contraction due to capacitative Ca(2+) entry. Tyrosine kinase inhibitors, genistein and tyrphostin 47 but not herbimycin A, suppressed the responses to Ca(2+)-reintroduction much greater than Ca(2+)-release responses to carbachol or caffeine. Similar inhibitory effects on the responses to Ca(2+)-reintroduction were obtained with daidzein and tyrphostin A1, respective inactive analogue of genistein and tyrphostins. After continuous depletion of the stores with thapsigargin, Ca(2+)-reintroduction produced a sustained contraction, which was inhibited by these agents to different extents, but not by herbimycin A. In beta-escin-treated skinned muscles, genistein slightly reduced Ca(2+)-induced contraction. In fura-2-loaded tissues, SK&F 96365 inhibited contractile and [Ca(2+)](i) responses to Ca(2+)-reintroduction but minimally affected Ca(2+)-release responses. Tetrandrine suppressed both responses to Ca(2+)-reintroduction and to Ca(2+)-release. These results suggest that genistein and tyrphostin 47 inhibit capacitative Ca(2+) entry through an inhibition of Ca(2+) entry channels rather than tyrosine kinase. SK&F 96365, but not tetrandrine, seems to selectively inhibit the contractile responses to capacitative Ca(2+) entry in rat ileal smooth muscles.
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