Renal mesangium is a target for calcitonin gene-related peptide

Kurtz, Armin; Schurek, H. J.; Jelkmann, Wolfgang; Muff, Roman; Lipp, Hans‐Peter; Heckmann, U; Eckardt, Kai‐Uwe; Scholz, Holger C.; Fischer, Jan A.; Bauer, Christian

doi:10.1038/ki.1989.183

Cited by 35 publications

(21 citation statements)

References 32 publications

(12 reference statements)

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“…In vitro CGRP blunts the contraction of mesangial cells obtained with angiotensin II [30]. Relaxation of mesangial cells by CGRP is consistent with the increased filtration fraction observed in vivo and in vitro.…”

Section: Renovascular Effectssupporting

confidence: 63%

“…In man and rabbits systemic infusion of CGRP reduces arterial pressure, and effective renal plasma and blood flow [4,29]. Since in vivo reduction of arterial pressure may reduce renal blood flow, effects of CGRP on the isolated rat kidney perfused at constant pressure have also been examined [30]. In this preparation rat CGRP-e reduces vascular resistance and blunts the vasoconstrictory effect of angiotensin II.…”

Section: Renovascular Effectsmentioning

confidence: 99%

“…In this preparation rat CGRP-e reduces vascular resistance and blunts the vasoconstrictory effect of angiotensin II. In the isolated perfused rat kidney CGRP moreover increases the glomerular filtration rate and the glomerular filtration fraction and urinary flow [30].…”

Section: Renovascular Effectsmentioning

confidence: 99%

“…Evidence was obtained that CGRP does not interfere with the calcium mobilization by angiotensin II in mesangial cells, suggesting that the dilatory effect of CGRP is caused by other mechanisms e.g. inactivation of the myosin light chain kinase [1,30].…”

Section: Renovascular Effectsmentioning

confidence: 99%

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Calcitonin gene products and the kidney

1989

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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...

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Section: Renovascular Effectssupporting

confidence: 63%

Section: Renovascular Effectsmentioning

confidence: 99%

Section: Renovascular Effectsmentioning

confidence: 99%

Section: Renovascular Effectsmentioning

confidence: 99%

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Calcitonin gene products and the kidney

1989

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“…The differential action of the two CGRPs was also recognizable with the stimulation of the plasma renin activity. Renin activity was stimulated directly in the isolated rat kidney perfused at constant pressure and in isolated rat juxtaglomerular cells (20,21). This effect is mediated through the protein kinase A pathway (20).…”

Section: Resultsmentioning

confidence: 99%

Distinct hemodynamic and gastric effects of human CGRP I and II in man

et al. 1991

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Distinct hemodynamic and gastric effects of human CGRP I and H in man. PEPTIDES 12(6) [1347][1348][1349][1350][1351] 1991.--The human calcitonin gene-related peptides I and II (or ct and 13) (CGRP I and II) are encoded by two different genes, but they have 34 of the 37 amino acid residues in common. Human CGRP I more potently stimulated blood flow through the skin and carotid artery (p<0.01), and the heart rate (p<0.05), and plasma renin activity and aldosterone secretion than human CGRP H (p<0.02). Inhibition of pentagastrin-stimulated gastric acid output, on the other hand, was only obtained with CGRP II. The separate effects of human CGRP I and I1 on the cardiovascular and gastric systems are presumably mediated by different receptors or receptor pathways recognized by the two closely related neuropeptides. AldosteroneCalcitonin gene-related peptide Gastric acid secretion Renin activity Vasodilatation HUMAN and rat calcitonin gene-related peptides I and II (or ct and 13) (CGRP I and II) differ in only 3 and 1 of the 37 amino acid residues, respectively (1,31). They are products of two separate genes. In man, the two genes are located on the same chromosome 11 and may have arisen by gene duplication (31). The relative expression of human CGRP I and II at the level of mRNA and mature peptides varies in different tissues (6,15,28, 34,35). CGRP exerts profound effects on the cardiovascular system of man and experimental animals, which include vasodilatation, positive chronotropic and ionotropic actions on the heart, and stimulation of plasma renin activity (5, 9-11, 20, 32). The latter effect represents a counterregulatory mechanism to the hypotension evoked by CGRP, but CGRP also directly stimulated the release of renin from juxtaglomerular cells (20). CGRP, moreover, inhibits gastric acid secretion with unchanged mucosal blood flow (19,22,23,33). We have reported earlier that human CGRP II, unlike CGRP I, inhibits pentagastrin-stimulated acid output (3).To address other potentially different biological targets of human CGRP I and II, we have now compared the cardiovascular effects of the two CGRPs, and have reexamined the inhibition of gastric acid output. The results provide evidence that human CGRP I more potently stimulates blood flow in the skin and the common carotid artery, and plasma renin activity and aldosterone levels than CGRP II, but does not suppress gastric acid secretion.1Requests for reprints should be addressed to Dr. J. A. Fischer, Klinik METHOD PeptidesSynthetic human CGRP I and II (or a and 13) were purchased from Peninsula Laboratories (Belmont, CA). Over 95% of the immunoreactive material eluted as a single peak on reversedphase HPLC (28). The CGRP was dissolved in 0.15 M NaC1 containing 0.1% human serum albumin, and vials containing 6.6 nmol/ml were prepared under aseptic conditions by the University of Basel Hospital Pharmacy and were stored at -20°C. The concentration of CGRP peptides obtained by weighing and by radioimmunoassay was within 10% of the predicted values.Pentagastrin (Pep...

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C1‐Inhibitor to Choriogonadotropin

Haeberli¹

1998

Human Protein Data

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Renal mesangium is a target for calcitonin gene-related peptide

Cited by 35 publications

References 32 publications

Calcitonin gene products and the kidney

Calcitonin gene products and the kidney

Distinct hemodynamic and gastric effects of human CGRP I and II in man

C1‐Inhibitor to Choriogonadotropin

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