Alterations of Cyclooxygenase-1, 2 Expression in Hypokalemic Rat Kidney / 대한해부학회지

ABSTRACT

A number of acid-base or electrolyte disorders are associated with decreased or increased HCO3- reabsorption in the renal tubules. There has been a general agreement that potassium depletion induces metabolic alkalosis and affects the expression of the several ion transporters in rats. The present study was to examine the alterations of expression and distribution of COX-1, 2 mRNAs and proteins in the kidneys of normal and K-depleted rats using RT-PCR, Western blot analysis, and immunohistochemistry. Predicted size of COX-1 mRNA was 306 bp. It's expression was increased in K-depleted rats, particularly LK 2W, but decreased in LK 3D. Predicted size of COX-2 mRNA was 356 bp and it's expression was increased in K-depleted rats, particularly LK 2W. Western blot analysis demonstrated that COX-1 protein, ~70 kDa at molecular mass, was increased in potassium-depleted rats, particularly LK 2W and decreased in LK 3D, compared with normal rat. COX-2 protein, ~72 kDa at molecular mass, was only increased in LK 3D and others were comparable with normal rat. In immunohistochemistry, COX-1 was detected in entire collecting duct, intraglomerular mesangial cells, arterial endothelial cells, medullary interstitial cells, papillary epithelial cells, and pelvic epithelium. Signal intensity of the collecting duct was more increased toward the papillary tip. In K-depleted rat, the pattern of cellular labeling of COX-1 protein was identical to that of normal rat. However, the signal intensity of LK 3D was only decreased in cortical and outer medullary collecting duct and that of LK 2W was increased particularly in the inner stripe of outer medullary collecting duct and proximal 1/3 inner medullary collecting duct. Immunoreactivity of COX-2 of normal rat was detected in the cortical thick ascending limb and macula densa. In K-depleted rat, the pattern of cellular labeling of COX-2 protein was identical to that of normal rat, but the signal intensity was only increased in LK 3D rat. These results suggest that chronic hypokalemia enhances the expression of COX-1, 2 mRNAs and proteins and the regulation of K reabsorption depends on COX-1 rather than COX-2 by the portions of expression.