CGRP Activates Renal Pelvic Substance P Receptors by Retarding Substance P Metabolism

Substance P and calcitonin gene-related peptide (CGRP) are colocalized in renal pelvic sensory nerves. Increasing renal pelvic pressure results in an increase in afferent renal nerve activity that is blocked by a substance P receptor antagonist but not by a CGRP receptor antagonist. CGRP potentiates the effects of substance P by preventing the metabolism of substance P. Therefore, we examined whether CGRP enhanced the afferent renal nerve activity responses to substance P and increased renal pelvic pressure, a stimulus known to increase substance P release. Combined administration of substance P and CGRP into the renal pelvis resulted in an increase in afferent renal nerve activity (1392 +/- 217% [middle dot] s; area under the curve of afferent renal nerve activity versus time) that was greater (P