Airway smooth muscle relaxation results from a reduction in the frequency of Ca2+ oscillations induced by a cAMP-mediated inhibition of the IP3 receptor.
Airway smooth muscle relaxation results from a reduction in the frequency of Ca2+ oscillations induced by a cAMP-mediated inhibition of the IP3 receptor.
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气道平滑肌松弛是由于CAMP介导的IP3受体抑制引起的Ca2+振荡频率的降低而导致的。
DOI：
10.1186/1465-9921-7-34
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发表时间：
2006-02-23
影响因子：
5.8
通讯作者：
Sanderson, MJ
中科院分区：
文献类型：
--
作者：
Bai, Y;Sanderson, MJ
已有研究表明，气道平滑肌细胞(SMC)对激动剂的收缩状态是由SMC内钙振荡的频率决定的。因此，我们推测，增加cAMP的药物引起的气道SMC的松弛是由于下调或减慢了钙振荡的频率所致。用相差显微镜和激光扫描显微镜观察了异丙肾上腺素(ISO)、福司可林(FSK)和8-溴环腺苷(8-bromo-cAMP)对小鼠肺切片上乙酰甲胆碱(MCH)收缩的气道SMC松弛和钙信号的影响。三种cAMP升高剂同时引起SMC内Ca~(2+)振荡频率的降低和收缩气道的松弛。Ca~(2+)振荡频率的降低与气道松弛程度相关，且呈浓度依赖性。探讨了cAMP降低钙振荡频率的机制。CAMP升高不影响重复接触20 mM咖啡因排空后体内钙离子储存区的再充盈率。升高的cAMP也没有限制可用于刺激收缩的Ca~(2+)，因为暴露于Ca~(2+)离子载体(离子霉素)或笼状Ca~(2+)光解引起的细胞内Ca~(2+)浓度的升高并不逆转cAMP的作用。钙激活K+通道的阻断剂伊贝里奥毒素也得到了类似的结果，预计它将增加钙离子的内流和收缩。相反，Cage-IP3在激动剂存在下的光解，进一步提高了细胞内IP3的浓度，逆转了FSK引起的Ca~(2+)振荡频率的减慢和气道的松弛。这一结果表明，FSK降低了IP3R对IP3的敏感性，而在FSK存在的情况下，IP3释放Ca~(2+)的能力降低也支持这一点。这些结果表明，cAMP升高剂对气道SMC的松弛作用是通过IP3受体减少内钙释放，从而降低细胞内钙振荡频率而实现的。
It has been shown that the contractile state of airway smooth muscle cells (SMCs) in response to agonists is determined by the frequency of Ca2+ oscillations occurring within the SMCs. Therefore, we hypothesized that the relaxation of airway SMCs induced by agents that increase cAMP results from the down-regulation or slowing of the frequency of the Ca2+ oscillations. The effects of isoproterenol (ISO), forskolin (FSK) and 8-bromo-cAMP on the relaxation and Ca2+ signaling of airway SMCs contracted with methacholine (MCh) was investigated in murine lung slices with phase-contrast and laser scanning microscopy. All three cAMP-elevating agents simultaneously induced a reduction in the frequency of Ca2+ oscillations within the SMCs and the relaxation of contracted airways. The decrease in the Ca2+ oscillation frequency correlated with the extent of airway relaxation and was concentration-dependent. The mechanism by which cAMP reduced the frequency of the Ca2+ oscillations was investigated. Elevated cAMP did not affect the re-filling rate of the internal Ca2+ stores after emptying by repetitive exposure to 20 mM caffeine. Neither did elevated cAMP limit the Ca2+ available to stimulate contraction because an elevation of intracellular Ca2+ concentration induced by exposure to a Ca2+ ionophore (ionomycin) or by photolysis of caged-Ca2+ did not reverse the effect of cAMP. Similar results were obtained with iberiotoxin, a blocker of Ca2+-activated K+ channels, which would be expected to increase Ca2+ influx and contraction. By contrast, the photolysis of caged-IP3 in the presence of agonist, to further elevate the intracellular IP3 concentration, reversed the slowing of the frequency of the Ca2+ oscillations and relaxation of the airway induced by FSK. This result implied that the sensitivity of the IP3R to IP3 was reduced by FSK and this was supported by the reduced ability of IP3 to release Ca2+ in SMCs in the presence of FSK. These results indicate that the relaxant effect of cAMP-elevating agents on airway SMCs is achieved by decreasing the Ca2+ oscillation frequency by reducing internal Ca2+ release through IP3 receptors.
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影响因子：
24.3
作者：
Hall, IP
通讯作者：
Hall, IP
影响因子：
4.8
作者：
Ding, KH;Husain, S;AbdelLatif, AA
通讯作者：
AbdelLatif, AA
DOI：
10.1152/ajplung.00043.2003
发表时间：
2003-12-01
影响因子：
4.9
作者：
Kuo, KH;Dai, JZ;van Breemen, C
通讯作者：
van Breemen, C
DOI：
10.1152/ajplung.00139.2002
发表时间：
2002-12-01
影响因子：
4.9
作者：
Bergner, A;Sanderson, MJ
通讯作者：
Sanderson, MJ
影响因子：
6
作者：
HALL, IP;DAYKIN, K;WIDDOP, S
通讯作者：
WIDDOP, S