Wang Z Y, Alm P, Håkanson R
Department of Pharmacology, University of Lund, Sweden.
Neuroscience. 1995 Nov;69(1):297-308. doi: 10.1016/0306-4522(95)00258-k.
Pituitary adenylate cyclase-activating peptide (PACAP)-like immunoreactivity was demonstrated by immunocytochemistry together with calcitonin gene-related peptide (CGRP)-like immunoreactivity in small to medium-sized neurons in the trigeminal ganglion and in nerve fibers in the iris, ciliary body, cornea, choroid and sclera of the rabbit eye. The regional distribution of PACAP-27- and PACAP-38-like immunoreactivity in the eye was studied by radioimmunoassay: the highest concentrations were found in the iris sphincter and ciliary body. The distribution pattern resembled that of CGRP-like immunoreactivity, which is a well-known constituent of sensory C-fibre neurons. Intravitreal injection of PACAP-27 or PACAP-38 induced conjunctival hyperemia, swelling of the anterior segment of the eye, miosis and breakdown of the blood-aqueous barrier, manifested as a marked aqueous flare response. Tetrodotoxin pretreatment inhibited the conjunctival hyperemia, the swelling of the anterior segment of the eye, and the miosis but not the aqueous flare response. The concentration of PACAP-like immunoreactivity in the aqueous humor was increased greatly following infrared irradiation of the iris, topical application of formaldehyde to the cornea, or intravitreal injection of endotoxin or bovine serum albumin. Also the concentration of CGRP-like immunoreactivity in the aqueous humor was increased greatly. Both in vivo and in vitro studies showed that capsaicin caused a parallel release of PACAP-like immunoreactivity and CGRP-like immunoreactivity from the uvea. Injection of PACAP-27 and PACAP-38 resulted in the release of CGRP-like immunoreactivity (and PACAP-like immunoreactivity) into the aqueous humor and PACAP-27 and PACAP-38 were also found to evoke tachykinin-mediated contractions of the isolated iris sphincter muscle, indicating that PACAP induces positive feedback on C-fibres. Thus, PACAP is a sensory neuropeptide in the eye. Since the PACAP-induced ocular responses mimicked the symptoms of inflammation, and since the PACAP-like immunoreactivity concentration in the aqueous humor was greatly increased following noxious stimulation, we suggest that it takes part in the inflammatory responses of the rabbit eye.
通过免疫细胞化学方法，在兔眼三叉神经节中小至中等大小的神经元以及虹膜、睫状体、角膜、脉络膜和巩膜的神经纤维中，证实了垂体腺苷酸环化酶激活肽（PACAP）样免疫反应性与降钙素基因相关肽（CGRP）样免疫反应性共存。采用放射免疫分析法研究了眼内PACAP - 27和PACAP - 38样免疫反应性的区域分布：在虹膜括约肌和睫状体中发现浓度最高。其分布模式类似于CGRP样免疫反应性的分布模式，CGRP是感觉C纤维神经元的一种众所周知的成分。玻璃体内注射PACAP - 27或PACAP - 38可引起结膜充血、眼前节肿胀、瞳孔缩小以及血 - 房水屏障破坏，表现为明显的房水闪光反应。河豚毒素预处理可抑制结膜充血、眼前节肿胀和瞳孔缩小，但不抑制房水闪光反应。虹膜红外线照射、角膜局部应用甲醛、玻璃体内注射内毒素或牛血清白蛋白后，房水中PACAP样免疫反应性浓度大幅升高。房水中CGRP样免疫反应性浓度也大幅升高。体内和体外研究均表明，辣椒素可使葡萄膜平行释放PACAP样免疫反应性和CGRP样免疫反应性。注射PACAP - 27和PACAP - 38可导致CGRP样免疫反应性（以及PACAP样免疫反应性）释放到房水中，并且还发现PACAP - 27和PACAP - 38可引起离体虹膜括约肌肌肉的速激肽介导的收缩，表明PACAP对C纤维诱导正反馈。因此，PACAP是眼中的一种感觉神经肽。由于PACAP诱导的眼部反应模拟了炎症症状，并且由于有害刺激后房水中PACAP样免疫反应性浓度大幅增加，我们认为它参与了兔眼的炎症反应。
