Modulation of gap junctions between retinal neurons by intracellular messengers.

细胞内注射环状GMP或可溶性鸟苷酸环化酶激活剂，如一氧化氮（NO）和花生四烯酸，可以关闭鲤鱼和海龟视网膜水平细胞之间的间隙连接。为了确定环GMP对间隙连接的阻断作用是否通过环GMP依赖性蛋白激酶的作用，我们通过注射蛋白激酶抑制剂检测了鲤鱼视网膜发光型水平（H1）细胞与路西法黄CH的染料偶联状态。在细胞内注射环GMP和环GMP-环amp依赖蛋白激酶a -3 （N-（2-氨基乙基）-5-氯萘-1-磺胺盐化物）的混合物后，水平细胞之间出现染料偶联。将环GMP与环GMP依赖性蛋白激酶抑制剂肽（Arg-Lys-Arg-Ala-Arg-Lys-Glu）的混合物注射到水平细胞后，也观察到染料偶联，表明抑制剂抑制了环GMP的解耦作用。同样的激酶抑制剂不抑制环AMP对间隙连接的解耦作用。另一方面，注射环状GMP和环状amp依赖性蛋白激酶抑制剂肽（arg - gly - tryala - leu - gly）的混合物后，单个细胞出现荧光。这些发现表明，环GMP对水平细胞间间隙连接通讯的阻断作用是通过环GMP依赖的蛋白激酶的作用，并且在水平细胞中，环GMP以一种独立于众所周知的多巴胺/环AMP途径的方式调节间隙连接。

Intracellular injection of cyclic GMP or soluble guanylate cyclase activators, such as nitric oxide (NO) and arachidonic acid, closed gap junctions between horizontal cells in carp (Cyprinus carpio) and turtle (Geoclemys reevesii) retinas. To determine whether the blocking effect of cyclic GMP on the gap junctions was through the action of cyclic GMP-dependent protein kinase, we examined the status of dye-coupling with Lucifer yellow CH among luminosity-type horizontal (H1) cells in the carp retina, by injection of protein kinase inhibitors into the cells. Dye-coupling among horizontal cells was observed after the intracellular injection of the mixture of cyclic GMP and a cyclic GMP-and cyclic AMP-dependent protein kinase, A-3 (N-(2-aminoethyl)-5-chloronaphthalene-1-sulfonamide hydrochloride). Dye-coupling was observed also after the injection of the mixture of cyclic GMP and cyclic GMP-dependent protein kinase inhibitor peptide (Arg-Lys-Arg-Ala-Arg-Lys-Glu) into the horizontal cell, indicating that the inhibitor suppressed the decoupling effect of cyclic GMP.The same kinase inhibitor did not suppress the decoupling effect of cyclic AMP on the gap junctions. On the other hand, a single cell was seen fluorescing after the injection of the mixture of cyclic GMP and cyclic AMP-dependent protein kinase inhibitor peptide (Arg-Gly-Try-Ala-Leu-Gly). These findings suggest that the blocking effct of cyclic GMP on gap-junctional intercellular communication among horizontal cells is through the action of cyclic GMP-dependent protein kinase, and that cyclic GMP modulates the gap junctions in a manner independent of the well-known dopamine/cyclic AMP pathway in the horizontal cell.