Chu T C, Candia O A
Department of Ophthalmology, Mount Sinai School of Medicine of the City University of New York, New York 10029.
Am J Physiol. 1988 Dec;255(6 Pt 1):C724-30. doi: 10.1152/ajpcell.1988.255.6.C724.
Norepinephrine, 10(-6) M, reduced Cl- transport by 26% in 75% of isolated frog corneal epithelia. This inhibition was not previously reported. Since beta-adrenergic agonists are known to only stimulate Cl- transport, the action of specific alpha 1- and alpha 2-agonists on Cl- transport and electrical parameters was investigated. Phenylephrine, an alpha 1-agonist always stimulated the Cl(-)-dependent short-circuit current (Isc), but less than the beta-agonists. UK-14,304-18 (UK), a selective alpha 2-agonist, reduced both the Isc (by 31% at 10(-5) M) and the stroma-to-tear unidirectional Cl- flux. UK hyperpolarized the apical membrane potential difference and increased the transepithelial resistance and apical-to-basolateral resistance ratio. UK reduced forskolin-stimulated adenylate cyclase activity by 36%. The electrophysiological effects of UK are consistent with a reduction of the Cl- permeability at the apical membrane. Pretreatment with UK sensitized the tissue for a greater effect by forskolin. Results show that the frog corneal epithelium also possesses alpha 1- and alpha 2-receptors, the latter negatively coupled to the adenylate cyclase system. Cl- transport is thus regulated by an interaction between the positive effects of beta- and alpha 1-stimulation and the negative influence of alpha 2-stimulation.
10⁻⁶ M的去甲肾上腺素使75%的离体蛙角膜上皮细胞的氯离子转运减少了26%。这种抑制作用此前未见报道。由于已知β-肾上腺素能激动剂仅刺激氯离子转运，因此研究了特异性α₁和α₂激动剂对氯离子转运和电参数的作用。α₁激动剂去氧肾上腺素总是刺激依赖氯离子的短路电流（Isc），但刺激程度小于β-激动剂。选择性α₂激动剂UK-14,304-18（UK）降低了Isc（在10⁻⁵ M时降低31%）以及基质到泪液的单向氯离子通量。UK使顶端膜电位差超极化，并增加了跨上皮电阻和顶端到基底外侧的电阻比。UK使福斯可林刺激的腺苷酸环化酶活性降低了36%。UK的电生理效应与顶端膜氯离子通透性降低一致。用UK预处理使组织对福斯可林的作用更敏感。结果表明，蛙角膜上皮细胞也具有α₁和α₂受体，后者与腺苷酸环化酶系统负偶联。因此，氯离子转运受β和α₁刺激的正向作用与α₂刺激的负向影响之间的相互作用调节。
