A new mechanism for the fine adjustment of pupil size : Relation with endogenous peptide

两种类型的对抗肌肉，括约肌和扩张肌，调节瞳孔的大小。虹膜括约肌与副交感神经支配成环状，当受刺激时，会引起瞳孔缩小。另一方面，虹膜扩张肌呈放射状，受交感神经支配，当受刺激时，引起瞳孔扩张。虹膜括约肌张力精细调节的机制在很大程度上是未知的。我们的研究结果首次证明，在分离的牛虹膜括约肌中，肾上腺髓质素（AM）以自分泌和旁分泌的方式降低肌肉的静息张力。其生物学效应可能是由于AM受体的直接参与，也可能是由于cgrp_1受体的刺激。肽刺激这些受体导致腺苷酸环化酶和可溶性鸟苷酸环化酶的激活和随后的肌条松弛。我们还发现肾上腺髓质素前n端12肽选择性地抑制烟碱能受体。此外，我们发现细胞质Ca^<2+>的增加诱导细胞表面Na^+通道的下调。

Two types of antagonistic muscles, the sphincter and the dilator ones, regulate the pupil size. This iris sphincter muscle is organized in a circular band with parasympathetic innervation which, when stimulated, causes miosis. On the other hand, the iris dilator muscle is oriented radially and innervated by the sympathetic nerves which, when stimulated, causes mydriasis. Mechanisms for the fine adjustment of the iris sphincter muscle tone are largely unknown. Our results demonstrate for the first time that in the isolated bovine iris sphincter muscle, adrenomedullin (AM) decreases resting tension of the muscle in an autocrine and paracrine manner. Its biological effects may be due to direct involvement of AM receptors, and also to stimulation of CGRP_1-receotirs. Stimulation of these receptors by the peptide lead to the activation of adenylate cyclase and soluble guanylate cyclase and subsequent relaxation of the muscle strip. We also found that proadrenomedullin N-terminal 12 peptide selectively inhibited the nicotinic cholinergic receptors. Furthermore, we found that the increase in cytoplasmic Ca^<2+> induced down-regulation of cell surface Na^+ chanel.