期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 280, 期 4, 页码 L666-L674出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.2001.280.4.L666
关键词
mitogen-activated protein kinase; norepinephrine; thromboxane A(2); intracellular calcium; protein kinase C; myosin light chain kinase; myosin light chain phosphatase
We investigated the mechanisms that underlie the responses to norepinephrine (NE) and thromboxane (Tx) A(2) (TxA(2))in the canine pulmonary vasculature with fura 2 fluorimetric, intracellular microelectrode, and force transduction techniques. KCl, caffeine, and cyclopiazonic acid elevated intracellular Ca2+ concentration levels and tone, indicating that Ca2+ mobilization is sufficient to produce contraction. However, contractions evoked by NE or the TxA(2) mimetic U-46619 were unaffected by nifedipine or by omitting external Ca2+ and were reduced only partially by depleting the internal Ca2+ store; furthermore, NE-evoked depolarization was subthreshold for voltage-dependent Ca2+ currents. Agonist-evoked contractions were insensitive to inhibitors of protein kinase C (calphostin C and chelerythrine), mitogen-activated protein kinase kinase (PD-98059), and p38 kinase (SB-203580) but were abolished by the tyrosine kinase inhibitor genistein and the Rho kinase inhibitor Y-27632. We conclude that, although Ca2+ influx and Ca2+ release are sufficient for contraction, they are not necessary for adrenergic or TxA(2) contractions. Instead, excitation-contraction coupling involves the activation of tyrosine kinase and Rho kinase, leading to enhanced Ca2+ sensitivity of the contractile apparatus.
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