The intrarenal site of calcitonin gene-related peptide degradation in the isolated perfused rat kidney.

Abstract

1. Calcitonin gene-related peptide (CGRP) is a potent vaso-active 37 amino acid peptide, typically elevated in plasma from patients with medullary thyroid cancer (MTC), but undetectable in the plasma of normal subjects. 2. The kidney is a major site for the clearance of exogenously infused CGRP but the intrarenal site of this clearance is unknown. Extra-organ clearance is also significant for CGRP, and whereas the site 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 vasculature 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 that (i) renal CGRP degradation occurs after glomerular filtration with intratubular metabolism and (ii) that there is no active CGRP degradation in the (glomerular) capillary endothelium. 4. These results do not support the theory that renal vascular endothelium plays a major active role in CGRP degradation.