Surgical sympathetic denervation increases alpha 1-adrenoceptor-mediated accumulation of myo-inositol trisphosphate and muscle contraction in rabbit iris dilator smooth muscle.
Surgical sympathetic denervation increases alpha 1-adrenoceptor-mediated accumulation of myo-inositol trisphosphate and muscle contraction in rabbit iris dilator smooth muscle.
复制标题
手术去交感神经增加了α1-肾上腺素受体介导的肌醇三磷酸的积累和兔虹膜扩张器平滑肌的肌肉收缩。
DOI：
10.1111/j.1471-4159.1986.tb12930.x
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发表时间：
1986
影响因子：
4.7
通讯作者：
Abdel-Latif,AA
中科院分区：
文献类型：
--
作者：
Akhtar,RA;Abdel-Latif,AA
虹膜肌肉的交感神经去支配导致磷酸肌醇4，5-二磷酸（PIP 2）的分解和对去甲肾上腺素（NE）的反应性肌肉收缩增加。为了更清楚地阐明这种超敏感性背后的生化基础，我们研究了：（1）NE对PIP的影响，分解，测量为三磷酸肌醇（IP 3）积累，并对正常和去神经支配的兔虹膜扩张肌的肌肉收缩;和（2）去神经支配对该肌肉的选定生化特性的影响。从这些研究中获得的数据可以总结如下：（1）在正常和去神经扩张肌中NE诱导的IP 3蓄积的EC 50值（μM）分别为14和3。1μM哌唑嗪可阻断IP 3的这种蓄积。(2)NE诱导的正常和失神经肌肉收缩的EC 50值（μM）分别为10和0.6。NE诱导的肌肉收缩被哌唑嗪（1μM）阻断。(3)正常和失神经肌肉中IP 3积累的t1/2值分别为31和11，收缩的t1/2值分别为19和9。(4)去神经支配显著增加（15-18%）来自肌-[3 H]肌醇的磷酸肌醇的基底标记，但不增加来自32 P或[14 C]花生四烯酸的磷酸肌醇的基底标记。(5)失神经支配对参与肌醇磷酸代谢的酶的活性影响不大。而失神经肌肉中蛋白激酶C和Ca 2 +-ATP酶活性升高。结论：虹膜扩张器的交感神经去支配使α 1受体和PIP 2之间的偶联更有效地分解为IP 3和1，2-二酰甘油（DG）。NE刺激的PIP 2的水解然后可以直接通过引起质膜去极化或间接通过IP 3从肌浆网释放Ca 2+和DG激活蛋白激酶C或两者来引起Ca 2+动员，这是肌肉收缩所必需的。
Sympathetic denervation of the iris muscle produces increases in both the breakdown of phosphati‐dylinositol 4,5‐bisphosphate (PIP2) and in muscle contraction in response to norepinephrine (NE). To shed more light on the biochemical basis underlying this supersensitivity we investigated: (1) the effects of NE on PIP, breakdown, measured as myoinositol trisphosphate (IP3) accumulation, and on muscle contraction in normal and denervated rabbit iris dilator; and (2) the effects of denervation on selected biochemical properties of this muscle. The data obtained from these studies can be summarized as follows: (1) The EC50values (μM) for NE‐induced IP3accumulation in normal and denervated dilators were 14 and 3, respectively. This accumulation of IP3was blocked by prazosin (1μM). (2) The EC50values (μM) for NE‐induced contraction for the normal and denervated muscles were 10 and 0.6, respectively. The NE‐induced muscle contraction was blocked by prazosin (1μM). (3) The t1/2values (s) for IP3accumulation in normal and denervated muscles were 31 and 11, respectively, and for contraction the values were 19 and 9, respectively. (4) Denervation increased significantly (15–18%) the basallabelling of phosphoinositides frommyo‐[3H]inositol, but not from32P or [14C]arachidonic acid. (5) Denervation had little effect on the activities of the enzymes involved in phosphoinositide metabolism. However, the activities of protein kinase C and Ca2+‐ATPase increased in the denervated muscle. It is concluded that sympathetic denervation of the iris dilator renders the coupling between α1receptors and PIP2breakdown into IP3and 1,2‐diacylglycerol (DG) more efficient. The NE‐stimulated hydrolysis of PIP2could then bring about Ca2+mobilization, necessary for muscle contraction, either directly by causing plasma membrane depolarization or indirectly by IP3releasing Ca2+from sarcoplasmic reticulum and by DG activating protein kinase C, or both.