Light-Mediated Inhibition of Colonic Smooth Muscle Constriction and Colonic Motility via Opsin 3.

Light-Mediated Inhibition of Colonic Smooth Muscle Constriction and Colonic Motility via Opsin 3.
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DOI:
10.3389/fphys.2021.744294
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发表时间:
2021
影响因子:
4
通讯作者:
Yim PD
Yim PD
中科院分区:
医学2区
文献类型:
--
作者:
Dan W;Park GH;Vemaraju S;Wu AD;Perez K;Rao M;Berkowitz DE;Lang RA;Yim PD

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中枢神经系统外的视蛋白光感受器已被证明介导几个器官中的平滑肌光松弛。我们假设结肠中的视蛋白受体活化将具有类似的作用并影响结肠运动。我们检测了Opsin 3(OPN 3)蛋白在结肠壁中的表达,并证明OPN 3存在于小鼠结肠固有肌层的肠神经元中。预收缩的鼠结肠段表现出蓝光(BL)介导的离体松弛。这种光弛豫是波长特异性的,并且随着发色团9-顺式视网膜和G蛋白受体激酶2(GRK 2)抑制剂的施用而增加。L-NAME或河豚毒素(TTX)不抑制光介导的结肠舒张。此外,BL暴露在9-顺式视网膜的存在下,结肠迁移运动复合体(CMMC)在自发收缩小鼠结肠离体的频率降低。这些结果首次证实了受体介导的结肠平滑肌光松弛,并暗示视蛋白可能成为治疗痉挛性胃肠动力障碍的新靶点。
Opsin photoreceptors outside of the central nervous system have been shown to mediate smooth muscle photorelaxation in several organs. We hypothesized that opsin receptor activation in the colon would have a similar effect and influence colonic motility. We detected Opsin 3 (OPN3) protein expression in the colonic wall and demonstrated that OPN3 was present in enteric neurons in the muscularis propria of the murine colon. Precontracted murine colon segments demonstrated blue light (BL) -mediated relaxation ex vivo. This photorelaxation was wavelength specific and was increased with the administration of the chromophore 9-cis retinal and a G protein receptor kinase 2 (GRK2) inhibitor. Light-mediated relaxation of the colon was not inhibited by L-NAME or tetrodotoxin (TTX). Furthermore, BL exposure in the presence of 9-cis retinal decreased the frequency of colonic migrating motor complexes (CMMC) in spontaneously contracting mouse colons ex vivo. These results demonstrate for the first time a receptor-mediated photorelaxation of colonic smooth muscle and implicate opsins as possible new targets in the treatment of spasmodic gastrointestinal dysmotility.
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