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Studies on endothelin release and Na,K transport in porcine lens.

Abstract：

PURPOSE:In an earlier study it was reported that thrombin significantly reduces the rate of Na,K-adenosine triphosphatase (ATPase)-mediated ion transport by porcine lens. Because thrombin stimulates the release of endogenous endothelin (ET)-1 stores from some tissues, and because ET-1 can cause Na,K-ATPase inhibition, this study was designed to determine whether thrombin causes release of ET-1 from the lens. METHODS:Intact porcine lenses were incubated in Krebs solution. The concentration of ET-1 in the solution was determined by ELISA. The rate of Na,K-ATPase-dependent ion transport was determined by measurement of ouabain-sensitive (86)Rb uptake. RESULTS:Thrombin (1 U/mL) reduced the rate of ouabain-sensitive (86)Rb uptake by approximately 40%. PD145065 (2 microM), an ET receptor antagonist, abolished the inhibitory effect of thrombin on (86)Rb uptake. Added alone, PD145065 did not alter (86)Rb uptake. After an incubation period of 30 minutes, thrombin increased the concentration of ET-1 in the bathing medium in a dose-dependent manner. The time course of ET-1 appearance in the bathing medium of thrombin-treated lenses showed a peak at 30 minutes followed by a gradual decline. Consistent with the idea that release of ET-1 from the lens is tightly regulated, neither the calcium ionophore A23187 (1 microM) nor depolarization by potassium-rich solution caused significant release. However, exposing the lens to insulin (150 nM) significantly increased the appearance of ET-1 in the bathing medium. In parallel studies, mRNA for prepro-ET-1 was detected in the epithelium of freshly isolated lenses. CONCLUSIONS:The results of the study suggest that ET-1 is produced in porcine lens cells and that thrombin and insulin are capable of stimulating the release of ET-1 from the lens. Thrombin-induced inhibition of Na,K-ATPase-dependent ion transport may be mediated in part through the activation of ET-1 receptors by ET-1 released from the lens.

journal_name

Invest Ophthalmol Vis Sci

journal_title

Investigative ophthalmology & visual science

authors

Okafor MC,Mukhopadhyay P,Delamere NA

keywords:

subject

Has Abstract

pub_date

2002-03-01 00:00:00

pages

790-6

issue

eissn

0146-0404

issn

1552-5783

journal_volume

pub_type

杂志文章

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Studies on endothelin release and Na,K transport in porcine lens.