环磷酸腺苷（cAMP）对猪睫状跨上皮短路电流、钠转运和氯转运的影响。

Effect of cAMP on porcine ciliary transepithelial short-circuit current, sodium transport, and chloride transport.

作者信息

Ni Ying, Wu Renyi, Xu Wen, Maecke Helmut, Flammer Josef, Haefliger Ivan O

机构信息

Laboratory of Ocular Pharmacology and Physiology, University Eye Hospital Basel, Basel, Switzerland.

出版信息

Invest Ophthalmol Vis Sci. 2006 May;47(5):2065-74. doi: 10.1167/iovs.05-0228.

DOI:10.1167/iovs.05-0228

PMID:16639017

Abstract

PURPOSE

To investigate the effects of 8-bromo-cAMP (cAMP) on porcine ciliary transepithelial short-circuit current (Isc) and transport of chloride (Cl-) and sodium (Na+).

METHODS

With Ussing-type chambers, cAMP-induced changes in Isc, electrical resistance (ER), and transepithelial 36Cl- and 22Na+ fluxes were measured. Drugs were applied to the nonpigmented epithelium (NPE) and/or pigmented epithelium (PE) side(s). The effect of IBMX (1, 5, or 10 microM; 3-isobutyl-1-methylxanthine) on Isc-increase induced by 8-bromo-cAMP on the PE side was also tested.

RESULTS

On the NPE side, a single concentration (10 microM, 100 microM, or 1 mM) of 8-bromo-cAMP induced a biphasic (transient peak followed by sustained plateau) Isc increase. On the PE side, 8-bromo-cAMP induced a similar but delayed biphasic Isc increase at 1 mM, a slight plateau-Isc increase at 100 microM, and no Isc increase at 10 microM. In the concentration-response curve, the cAMP-induced peak-Isc increase became significant at a concentration 10,000 times lower on the NPE than on the PE side. At 10 microM, the cumulative cAMP-induced Isc-increase reached its maximum on the NPE side, but was virtually nonexistent on the PE side. IBMX (a phosphodiesterase inhibitor) but not 8-CPT-6-Phe-cAMP (higher permeability than 8-bromo-cAMP) significantly increased the peak-Isc concentration-response curve induced by 8-bromo-cAMP (10 nM-1 mM) on the PE side. On the NPE but not the PE side, 10 microM 8-bromo-cAMP induced a significant but transient increase in net PE-to-NPE 36Cl- flux (1.03 +/- 0.18 microEq/min per square centimeter; P < 0.001). Neither ER nor transepithelial 22Na+ flux was changed after cAMP exposure.

CONCLUSIONS

In porcine ciliary processes, apparently on the NPE side, cAMP triggers a biphasic (transient peak followed by a sustained plateau) Isc increase. Only the peak-Isc increase involves an increase in net PE-to-NPE Cl- transport.

摘要

目的

研究8-溴环磷腺苷（cAMP）对猪睫状体跨上皮短路电流（Isc）以及氯离子（Cl-）和钠离子（Na+）转运的影响。

方法

使用Ussing型小室，测量cAMP诱导的Isc、电阻（ER）以及跨上皮36Cl-和22Na+通量的变化。药物施加于非色素上皮（NPE）和/或色素上皮（PE）侧。还测试了1,5-异丁基-1-甲基黄嘌呤（IBMX，1、5或10微摩尔）对PE侧8-溴环磷腺苷诱导的Isc增加的影响。

结果

在NPE侧，单一浓度（10微摩尔、100微摩尔或1毫摩尔）的8-溴环磷腺苷诱导Isc呈双相增加（短暂峰值后接着持续平台期）。在PE侧，1毫摩尔的8-溴环磷腺苷诱导类似但延迟的双相Isc增加，100微摩尔时Isc有轻微的平台期增加，10微摩尔时无Isc增加。在浓度-反应曲线中，cAMP诱导的峰值Isc增加在NPE侧的浓度比PE侧低10000倍时变得显著。在10微摩尔时，累积的cAMP诱导的Isc增加在NPE侧达到最大值，但在PE侧几乎不存在。IBMX（一种磷酸二酯酶抑制剂）而非8-CPT-6-Phe-cAMP（通透性高于8-溴环磷腺苷）显著增加了PE侧8-溴环磷腺苷（10纳摩尔至1毫摩尔）诱导的峰值Isc浓度-反应曲线。在NPE侧而非PE侧，10微摩尔的8-溴环磷腺苷诱导净PE到NPE的36Cl-通量显著但短暂增加（1.03±0.18微当量/分钟每平方厘米；P<0.001）。cAMP暴露后，ER和跨上皮22Na+通量均未改变。