THE INTRARENAL SITE OF CALCITONIN-GENE-RELATED PEPTIDE DEGRADATION INTHE ISOLATED-PERFUSED RAT-KIDNEY

1. Calcitonin gene-related peptide (CGRP) is a potent vaso-active 37 a mino acid peptide, typically elevated in plasma from patients with med ullary thyroid cancer (MTC), but undetectable in the plasma of normal subjects. 2. The kidney is a major site for the clearance of exogenous ly infused CGRP but the intrarenal site of this clearance is unknown. Extra-organ clearance is also significant for CGRP, and whereas the si te and mechanism of this degradation remain uncertain, the vasculature has been postulated as the most likely site. 3. The isolated perfused rat kidney (IPRK) was studied to (i) localize the intrarenal site of CGRP clearance and (ii) determine the contribution of the renal vascul ature to the clearance of CGRP. The half-life of CGRP in the filtering IPRK was 63.9+/-4.5 min, whereas blocking of filtration by elevation of the perfusate osmolarity abolished the degradation. This suggests t hat (i) renal CGRP degradation occurs after glomerular filtration with intratubular metabolism and (ii) that there is no active CGRP degrada tion in the (glomerular) capillary endothelium. 4. These results do no t support the theory that renal vascular endothelium plays a major act ive role in CGRP degradation.