DIFFERENTIAL EXPRESSION OF MESSENGER-RNA FOR GUANYLYL CYCLASE-LINKED ENDOTHELIUM-DERIVED RELAXING FACTOR RECEPTOR SUBUNITS IN RAT-KIDNEY

Endothelium-derived relaxing factor (EDRF) has profound effects on the renal vasculature, the glomerular mesangium, and also affects renal salt excretion. EDRF stimulates guanylyl cyclases, which are thought to be heterodimers comprised of alpha and beta subunits. Two alpha and two beta isoforms have been identified thus far. However, the molecular composition of in vivo guanylyl cyclase-linked EDRF receptors is unknown. We used polymerase chain reaction to clone a portion of the rat alpha2 subunit. Guanylyl cyclase-linked EDRF receptor mRNA was detected in microdissected renal structures using a reverse transcription/polymerase chain reaction assay. The interlobular artery/afferent arteriole contained mRNA for the alpha1, alpha2, and beta1 subunits; a faint beta2 band was found in 29% of experiments. In contrast, the cortical collecting duct contained mRNA only for alpha1 and beta2 subunits. We conclude that guanylyl cyclase-linked EDRF receptor subunit isoforms are independently and heterogeneously expressed in the renal vasculature and cortical collecting duct, suggesting that several different EDRF receptors exist in vivo. These data suggest that the tubule receptor is composed of alpha1/beta2. The vasculature may contain at least two different EDRF receptors (alpha1/beta1 and alpha2/beta1). Some beta2 may also be expressed, allowing for even greater heterogeneity.