Calcitonin gene products and the kidney

Abstract

Summary. Calcitonin gene-related peptide (CGRP) is localized in capsaicin-sensitive nerve fibres in the kidney and urogenital tract whereas calcitonin reaches the kidney through the general circulation. Systemic infusion of CGRP and perfusion of isolated rat kidney reduces vascular resistance, and increases renal blood flow and glomerular filtration. CGRP stimulates renin secretion in vivo and in vitro and inhibits contraction of isolated rat mesangial cells by angiotensin II. Calcitonin does not affect vascular resistance, renal blood flow and glomerular filtration, and is tess potent in stimulating renin secretion, and does not alter contraction of isolated rat mesangial cells by angiotensin II. CGRP also exerts renal tubular effects brought about probably through interaction with calcitonin receptors. To this end, increased excretion of sodium and chloride, and stimulation of urinary flow are less pronounced with CGRP than with calcitonin. Calcitonin, moreover, stimulates the fractional urinary excretion of calcium and phosphate.Key words: Calcitonin -Calcitonin gene-related peptide -Renovascular effects -Renotubular effects -Renin secretion Alternative splicing of the initial calcitonin gene transcript results in the formation of two distinct messenger RNAs encoding the precursors of calcitonin and of calcitonin gene-related peptide (CGRP) [2,26]. In man and rat two calcitonin/ CGRP genes have been recognized [3,40]. A pseudogene encoding a second calcitonin-like structure appears not to be expressed in man [40]. But CGRP-I (or 7) and -II (or fl) have been identified in man and rat at the mRNA and peptide levels [3, 23, 341. Calcitonin and CGRP are single chain polypeptides consisting of 32 and 37 amino acids, respectively. They have in common amino-terminal ring structures linked by disulfide bridges and the carboxyltermini are amidated. In man, CGRP shares 16% structural homology with calcitonin whereas the homology between CGRP-I and -II is 92% [13]. As a result, distinct receptors for calcitonin and CGRP have been identified [7,11,33,42]. Human CGRP-I and -II, due to their high homology, crossreact almost completely, but subtle differences in the distribution of human CGRP-I and -II binding sites have been observed on receptor autoradiography of the human brain [22].Calcitonin is predominantly synthesized and released from thyroid C-cells [15]. An important stimulator of calcitonin secretion is an increase in the extracellular calcium concentration [36]. Calcitonin can be considered as a hormone that reaches its target tissues via the circulation. Calcitonin lowers serum calcium levels through inhibition of bone resorption [37]. In the kidney, calcitonin stimulates the urinary excretion of calcium, phosphate, sodium, potassium and chloride, and enhances 1,25-dihydroxycholecalciferol production [5,20,25,32].CGRP is predominantly synthesized in the nervous system and is frequently found in peripheral nerves associated with blood vessels, but CGRP has also been identified in the normal human thyroid glan...

The Renal Microcirculation

“…CGRP-induced vasodilation is mediated by CGRP1 receptors, localized on VSMC, modified by receptor activator modifying proteins (RAMP), with participation of EC, NO, and cAMP/PKA signaling [1771,1772] . CGRP stimulates renin secretion in vivo and in vitro and inhibits contraction of isolated rat mesangial cells by ANG II [1773] . Whereas the vascular actions are mediated in part by NO, the excretory responses are not affected by NOS inhibition [1769] .…”

The rat renal nerves during development

“…Nerves containing peptides, such as calcitonin gene-related peptide (CGRP) and substance P (SP), which serve as neurotransmitters in sensory nerves, have been immunolocalized in the kidney (Su et al 1986;Reinecke and Forssmann 1988;Geppetti et al 1989;Kurtz et al 1989; Barajas et al 1991;Knight et al 1991). CGRP-immunoreactive nerves (CGRP-IN) and substance P-immunoreactive nerves (SP-IN) have been demonstrated in the renal pelvis, vasculature, and the corticomedullary connective tissue.…”

Calcitonin gene-related peptide and its receptors: molecular genetics, physiology, pathophysiology, and therapeutic potentials

“…Also, the increase of i-CGRP during the presyncopal period and tilt studies suggests an active role of this peptide in peripheral vasorelaxation (546,547). and the fractional excretion of sodium and chloride in humans (424,548,549). Morphological studies conducted by Li and colleagues (550) show that treatment with CGRP can attenuate ischemic-reperfusion injury to renal brush borders and mitochrondria.…”