Di Salvo J, Steusloff A, Semenchuk L, Satoh S, Kolquist K, Pfitzer G
Department of Medical and Molecular Physiology, University of Minnesota-Duluth 55812.
Biochem Biophys Res Commun. 1993 Feb 15;190(3):968-74. doi: 10.1006/bbrc.1993.1144.
Because tyrosine kinases participate in diverse signalling pathways, we suspected that these enzymes might also participate in regulation of signal transduction in smooth muscle. Therefore, we studied the effects of geldanomycin, tyrphostin, and genistein, three structurally unrelated tyrosine kinase inhibitors, on receptor-mediated and depolarization-mediated contraction in three different types of smooth muscle. Contraction elicited by stimulation of muscarinic receptors with carbachol, or by stimulation of alpha-adrenergic receptors with norepinephrine or phenylephrine were markedly (> 80%) and reversibly inhibited by tyrosine-kinase inhibitors. In contrast, only slight inhibition (20%) occurred in contractions elicited by K(+)-induced depolorization. Moreover, tyrphostin did not inhibit direct Ca(2+)-mediated activation of the contractile apparatus in preparations permeabilized with beta-escin. These results suggest the novel hypothesis that tyrosine kinases participate in regulation of signal transduction that is associated with receptor-mediated contraction of smooth muscle.
由于酪氨酸激酶参与多种信号通路，我们推测这些酶可能也参与平滑肌信号转导的调控。因此，我们研究了格尔德霉素、 tyrphostin和染料木黄酮这三种结构不相关的酪氨酸激酶抑制剂，对三种不同类型平滑肌中受体介导和去极化介导的收缩的影响。用卡巴胆碱刺激毒蕈碱受体或用去甲肾上腺素或苯肾上腺素刺激α-肾上腺素能受体所引发的收缩，被酪氨酸激酶抑制剂显著（>80%）且可逆地抑制。相比之下，K⁺诱导的去极化所引发的收缩仅受到轻微抑制（20%）。此外，tyrphostin并不抑制用β-七叶皂苷通透处理的标本中由直接Ca²⁺介导的收缩装置激活。这些结果提示了一个新的假说，即酪氨酸激酶参与与平滑肌受体介导的收缩相关的信号转导调控。
