Tyrosine kinases regulate intracellular calcium during alpha(2)-adrenergic contraction in rat aorta.
Tyrosine kinases regulate intracellular calcium during alpha(2)-adrenergic contraction in rat aorta.
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酪氨酸激酶在大鼠主动脉α(2)-肾上腺素能收缩过程中调节细胞内钙。
DOI：
10.1152/ajpheart.01034.2001
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Kanagy,NancyL
中科院分区：
文献类型：
--
作者：
Carter,RebeccaW;Kanagy,NancyL
We have demonstrated enhanced contractile sensitivity to the α2-adrenoreceptor (α2-AR) agonist UK-14304 in arteries from rats made hypertensive with chronic nitric oxide synthase (NOS) inhibition (LHR) compared with arteries from normotensive rats (NR); additionally, this contraction requires Ca2+entry. We hypothesized that tyrosine kinases augment α2-AR contraction in LHR arteries by increasing Ca2+. The tyrosine kinase inhibitor tyrphostin 23 significantly attenuated UK-14304 contraction of denuded thoracic aortic rings from NR and LHR. However, tyrphostin 23 did not alter UK-14304 contraction in ionomycin-permeabilized aorta, which indicates that tyrosine kinases regulate intracellular Ca2+concentration. The Src family inhibitor PP1 and the epidermal growth factor receptor kinase inhibitor AG-1478 did not alter α2-AR contraction, whereas the mitogen-activated protein kinase extracellular signal-regulated kinase kinase inhibitor PD-98059 attenuated the contraction. Contraction to CaCl2in ionomycin-permeabilized LHR rings was greater than in NR rings. UK-14304 augmented CaCl2contraction in ionomycin-permeabilized rings from both groups but to a greater extent in LHR aorta. Together, these data suggest that α2-AR stimulates contraction via two pathways. One, which is enhanced with NOS inhibition hypertension, activates Ca2+sensitivity and is independent of tyrosine kinases. The other is tyrosine kinase dependent and regulates intracellular Ca2+concentration.
