RAT KIDNEY THROMBOXANE RECEPTOR - MOLECULAR-CLONING, SIGNAL-TRANSDUCTION, AND INTRARENAL EXPRESSION LOCALIZATION

Thromboxane (TX) plays important roles in control of renal hemodynamic s and water and electrolyte metabolism, and is involved in the pathoph ysiology of many renal diseases. The aim of the present study is to is olate a rat kidney cDNA encoding functional TX receptor, and to reveal its intrarenal expression localization, A clone (rTXR2) was isolated from a rat kidney cDNA library by a homology screening approach, rTXR2 was shown to encode the amino acid sequence containing seven transmem brane spanning domains representing rat (r) TX receptor. The membrane from COS-7 cells transiently transfected with rTXR2 cDNA was shown to be specifically bound by a thromboxane receptor antagonist, SQ29548. E ither in Xenopus oocyte expression or in transfected COS-7 cells, rTX receptor was shown to be linked with Ca2+ messenger system, TX recepto r-mediated increase in cytosolic Ca2+ was also observed in cultured gl omerular mesangial cells. In situ hybridization showed that rTX recept or mRNA was detected in renal glomeruli, smooth muscle cells in renal arterioles, and transitional cell epithelium of renal pelvis, Reverse transcription linked to PCR applied to microdissected nephron segments indicated the presence of rTX receptor mRNA exclusively in the glomer ulus. In conclusion, we have cloned a functional rat kidney TX recepto r, which is expressed specifically in renal glomerulus, arterial smoot h muscle cells, and transitional cell epithelium of renal pelvis, The present study will provide important insights into the etiology and pa thophysiology of renal diseases with relation to TX metabolism.