降钙素基因相关肽通过环磷酸腺苷依赖性机制使兔虹膜开大肌平滑肌松弛：感觉神经系统与交感神经系统之间的相互作用。
Calcitonin gene-related peptide relaxes rabbit iris dilator smooth muscle via cyclic AMP-dependent mechanisms: cross-talk between the sensory and sympathetic nervous systems.
作者信息
Yousufzai S Y, Abdel-Latif A A
机构信息
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912-2100, USA.
出版信息
Curr Eye Res. 1998 Feb;17(2):197-204. doi: 10.1076/ceyr.17.2.197.5605.
PURPOSE
The purpose of these studies is to determine whether or not cyclic AMP is involved in the relaxant action of calcitonin gene-related peptide (CGRP) in rabbit iris dilator muscle.
METHODS
Iris dilator muscle isolated from rabbit was used. Accumulation of cAMP and cGMP in the tissue extracts was measured by radioimmunoassay (RIA), IP3 production was measured by ion-exchange chromatography, and changes in tension were recorded isometrically.
RESULTS
CGRP, vasoactive intestinal peptide, prostaglandin E2, isoproterenol and forskolin (1 microM of each) increased cAMP accumulation by 136, 256, 78, 141 and 315%, respectively. CGRP dose-dependently increased cAMP accumulation (EC50 = 5.25 nM), inhibited IP3 production (EC50 = 5.4 nM) and induced relaxation (EC50 = 10 nM) in muscle precontracted with norepinephrine (NE) (10 microM). Prostaglandin E2, isoproterenol and forskolin also induced relaxation. CGRP stimulated cAMP formation either in the presence or absence of 3-isobutyl-1-methylxanthine (IBMX), a cAMP phosphodiesterase inhibitor, in a time- and concentration-dependent manner. The neuropeptide had no effect on cGMP accumulation. CGRP (8-37), a CGRP receptor antagonist, reversed the relaxant action of the neuropeptide and inhibited CGRP-induced cAMP accumulation in a concentration-dependent manner (IC50 = 12.5 nM). 2',5'-dideoxyadenosine (DDA), a specific adenylate cyclase inhibitor, significantly reduced the inhibitory actions of CGRP on NE-induced contraction and IP3 production and inhibited CGRP-induced cAMP accumulation in a concentration-dependent manner (IC50 = 6.9 nM).
CONCLUSIONS
These results strongly suggest that cAMP mediates the relaxant action of CGRP in rabbit iris dilator. The mechanism of cAMP inhibition of NE-induced IP3 production and contraction is unclear. Modulation of alpha 1-adrenergic function in the iris dilator by CGRP-induced cAMP formation is yet another example of cross-talk between the cAMP and IP3-Ca2+ second messenger systems, it demonstrates a cross-talk between the sympathetic and sensory nervous systems. CGRP-containing sensory nerve fibers could play an important role in regulation of smooth muscle function in the iris-ciliary body.
目的
这些研究的目的是确定环磷酸腺苷（cAMP）是否参与降钙素基因相关肽（CGRP）对兔虹膜开大肌的舒张作用。
方法
使用从兔分离的虹膜开大肌。通过放射免疫测定法（RIA）测量组织提取物中cAMP和环磷酸鸟苷（cGMP）的积累，通过离子交换色谱法测量肌醇三磷酸（IP3）的产生，并等长记录张力变化。
结果
CGRP、血管活性肠肽、前列腺素E2、异丙肾上腺素和福斯可林（每种1微摩尔）分别使cAMP积累增加136%、256%、78%、141%和315%。CGRP以剂量依赖性方式增加cAMP积累（半数有效浓度[EC50]=5.25纳摩尔），抑制IP3产生（EC50=5.4纳摩尔），并在与去甲肾上腺素（NE）（10微摩尔）预收缩的肌肉中诱导舒张（EC50=10纳摩尔）。前列腺素E2、异丙肾上腺素和福斯可林也诱导舒张。CGRP在存在或不存在cAMP磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤（IBMX）的情况下，均以时间和浓度依赖性方式刺激cAMP形成。该神经肽对cGMP积累无影响。CGRP受体拮抗剂CGRP（8-37）可逆转该神经肽的舒张作用，并以浓度依赖性方式抑制CGRP诱导的cAMP积累（半数抑制浓度[IC50]=12.5纳摩尔）。特异性腺苷酸环化酶抑制剂2'，5'-二脱氧腺苷（DDA）显著降低CGRP对NE诱导的收缩和IP3产生的抑制作用，并以浓度依赖性方式抑制CGRP诱导的cAMP积累（IC50=6.9纳摩尔）。
结论
这些结果强烈表明，cAMP介导CGRP对兔虹膜开大肌的舒张作用。cAMP抑制NE诱导的IP3产生和收缩的机制尚不清楚。CGRP诱导的cAMP形成对虹膜开大肌中α1肾上腺素能功能的调节是cAMP与IP3-Ca2+第二信使系统之间相互作用的又一个例子，它证明了交感神经系统和感觉神经系统之间的相互作用。含CGRP的感觉神经纤维可能在虹膜-睫状体平滑肌功能调节中起重要作用。
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