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Gene Review

Calcrl  -  calcitonin receptor-like

Rattus norvegicus

Synonyms: CGRP type 1 receptor, CLR, Calcitonin gene-related peptide type 1 receptor, Calcitonin receptor-like receptor, Cgrpr, ...
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Disease relevance of Calcrl

  • In the present study, we have examined gene expression of RAMP2, CRLR and adrenomedullin in hearts and kidneys of rats with congestive heart failure caused by coronary artery ligation [1].
  • To obtain structural and functional information on the Nt-CRLR, we cloned and expressed the Nt-CRLR as a fusion protein in Escherichia coli [2].
  • The gene expression of adrenomedullin, calcitonin-receptor-like receptor and receptor activity modifying proteins (RAMPs) in CCl4-induced rat liver cirrhosis [3].
  • Quinine levels in plasma and urine of the rats with induced renal failure were determined and pharmacokinetic parameters (elimination t1/2, CLp, V, CLR AUC0-infinity) of the drug were derived and compared with values obtained from control rats following intraperitoneal administration of a 10 mg/kg body-weight dose of quinine [4].

High impact information on Calcrl

  • Here, the amino acid sequence TRNKIMT, corresponding to the residues 14-20 of the N terminus of the mouse (m) CLR, was found to be required for a functional mCLR/RAMP2 AM receptor [5].
  • In support of a paracrine role for IMD in the pituitary, quantitative and in situ hybridization analyses showed the expression of IMD receptor transcripts including the calcitonin receptor-like receptor and receptor activity-modifying proteins in the pituitary [6].
  • AM mediates its effects through either AM(22-52)-sensitive AM1 receptors [composed of calcitonin receptor-like receptors (CLs) and receptor activity-modifying protein (RAMP)2] or AM2 receptors (CL/RAMP3), which can be antagonized more potently by calcitonin gene-related peptide(8-37) than AM(22-52) [7].
  • Several chimeric CLR-PTHR included the N-terminal amino acids 23-60 of the CLR transported RAMP1 to the surface of COS-7 cells much like the intact CLR [8].
  • In conclusion, structural elements in the extreme N-terminus of the CLR between amino acids 23-60 are required and sufficient for CLR/RAMP1 cotransport to the plasma membrane and heterodimerization [8].

Biological context of Calcrl

  • We investigated whether coexpression of RAMP and CRLR are involved in the regulation of cell migration using a monolayer-wounding protocol [9].
  • Our results show upregulation of RDC-1, RAMP1, and RAMP3 mRNAs in hypoxic rat lung and no change in CRLR and RAMP2 mRNAs [10].
  • RT-PCR analysis showed that mRNA expression of CRLR and RAMP(1) was significantly higher in the rat placenta from gestation day 17 to day 22, than during labour [11].
  • Elevated placental CRLR and RAMP(1) may be involved in CGRP-related increases in blood flow and therefore fetal growth and decreases at term labour may help minimize the blood loss [11].
  • These changes in binding sites appear to be related to the changes in calcitonin receptor-like receptor (CRLR), receptor activity-modified protein 1 (RAMP1), RAMP2, and RAMP3 mRNA levels [12].

Anatomical context of Calcrl


Associations of Calcrl with chemical compounds

  • In adult ovariectomized rats, progesterone caused significant increases in CRLR (P < 0.001), RAMP1 (P < 0.05), and RAMP2 (P < 0.01) [13].
  • Estradiol-17beta treatment decreased all of the four receptor components significantly (P < 0.01 for CRLR, P < 0.05 for RAMP1, RAMP2, and RAMP3) [13].
  • Antiestrogen, ICI 182780, increased, whereas antiprogesterone, RU 486, inhibited the expression of both CRLR and RAMP(1) [11].
  • These studies revealed that both CRLR and L1 were expressed only in cells that did not express PNMT, suggesting that adrenomedullin receptors are only found in noradrenaline-secreting cells [16].
  • Hydralazine/hydrochlorothiazide normalized systolic blood pressure (BP) and abolished mRNA up-regulation of hypertrophic markers sk-alpha-actin and BNP and of preproAM, CLR, RAMP2, and RAMP3 but did not normalize cardiomyocyte width nor preproIMD or RAMP1 mRNA expression [17].

Physical interactions of Calcrl


Other interactions of Calcrl

  • The elevated levels of CRLR, RAMP2 and RAMP3 mRNA were significant correlation with ADM mRNA (r = 0.83, 0.92 and 0.93, respectively, all p's < 0.01) in calcified VSMCs [21].
  • Coexpression of RAMP1 and CRLR resulted in functional CGRP1 receptors; the complex of RAMP2 or RAMP3 and CRLR created functional adrenomedullin receptor [15].
  • Western blot showed that protein expression for the calcitonin receptor-like receptor-but not receptor activity modifying protein 1, VR1, and cannabinoid type 1 receptors-was increased in mesenteric resistance arteries in SHR compared with WKY (P<0.05) [22].

Analytical, diagnostic and therapeutic context of Calcrl


  1. Increased gene expression of adrenomedullin and adrenomedullin-receptor complexes, receptor-activity modifying protein (RAMP)2 and calcitonin-receptor-like receptor (CRLR) in the hearts of rats with congestive heart failure. Totsune, K., Takahashi, K., Mackenzie, H.S., Murakami, O., Arihara, Z., Sone, M., Mouri, T., Brenner, B.M., Ito, S. Clin. Sci. (2000) [Pubmed]
  2. Role of the N-terminal domain of the calcitonin receptor-like receptor in ligand binding. Chauhan, M., Rajarathnam, K., Yallampalli, C. Biochemistry (2005) [Pubmed]
  3. The gene expression of adrenomedullin, calcitonin-receptor-like receptor and receptor activity modifying proteins (RAMPs) in CCl4-induced rat liver cirrhosis. Hwang, I.S., Tang, F., Leung, P.P., Li, Y.Y., Fan, S.T., Luk, J.M. Regul. Pept. (2006) [Pubmed]
  4. Disposition of quinine in rats with induced renal failure. Onyeji, C.O., Dixon, P.A., Ugwu, N.C. Pharmaceutisch weekblad. Scientific edition. (1992) [Pubmed]
  5. Selective inactivation of adrenomedullin over calcitonin gene-related peptide receptor function by the deletion of amino acids 14-20 of the mouse calcitonin-like receptor. Koller, D., Ittner, L.M., Muff, R., Husmann, K., Fischer, J.A., Born, W. J. Biol. Chem. (2004) [Pubmed]
  6. Intermedin functions as a pituitary paracrine factor regulating prolactin release. Lin Chang, C., Roh, J., Park, J.I., Klein, C., Cushman, N., Haberberger, R.V., Hsu, S.Y. Mol. Endocrinol. (2005) [Pubmed]
  7. Female sex steroids increase adrenomedullin-induced vasodilation by increasing the expression of adrenomedullin2 receptor components in rat mesenteric artery. Ross, G.R., Chauhan, M., Gangula, P.R., Reed, L., Thota, C., Yallampalli, C. Endocrinology (2006) [Pubmed]
  8. The N-terminal extracellular domain 23-60 of the calcitonin receptor-like receptor in chimeras with the parathyroid hormone receptor mediates association with receptor activity-modifying protein 1. Ittner, L.M., Koller, D., Muff, R., Fischer, J.A., Born, W. Biochemistry (2005) [Pubmed]
  9. Coexpression of calcitonin receptor-like receptor and receptor activity-modifying protein 2 or 3 mediates the antimigratory effect of adrenomedullin. Fukai, N., Shichiri, M., Ozawa, N., Matsushita, M., Hirata, Y. Endocrinology (2003) [Pubmed]
  10. mRNA expression of novel CGRP1 receptors and their activity-modifying proteins in hypoxic rat lung. Qing, X., Svaren, J., Keith, I.M. Am. J. Physiol. Lung Cell Mol. Physiol. (2001) [Pubmed]
  11. Expression of calcitonin gene-related peptide receptor components, calcitonin receptor-like receptor and receptor activity modifying protein 1, in the rat placenta during pregnancy and their cellular localization. Dong, Y.L., Vegiraju, S., Chauhan, M., Yallampalli, C. Mol. Hum. Reprod. (2003) [Pubmed]
  12. Progesterone upregulates calcitonin gene-related peptide and adrenomedullin receptor components and cyclic adenosine 3'5'-monophosphate generation in Eker rat uterine smooth muscle cell line. Thota, C., Yallampalli, C. Biol. Reprod. (2005) [Pubmed]
  13. Changes in the expression of calcitonin receptor-like receptor, receptor activity-modifying protein (RAMP) 1, RAMP2, and RAMP3 in rat uterus during pregnancy, labor, and by steroid hormone treatments. Thota, C., Gangula, P.R., Dong, Y.L., Yallampalli, C. Biol. Reprod. (2003) [Pubmed]
  14. The expression of mRNA for calcitonin receptor-like receptor/receptor-activity modifying proteins in rat peritoneal mast cells. Matsushima, M., Kitaichi, K., Tatsumi, Y., Hasegawa, T., Takagi, K. Eur. J. Pharmacol. (2003) [Pubmed]
  15. Expression of calcitonin gene-related peptide type 1 receptor mRNA and their activity-modifying proteins in the rat nucleus accumbens. Li, N., Fang, C.Y., Wang, Z.Z., Wang, Y.L., Wang, F.B., Gao, E., Zhang, G.X. Neurosci. Lett. (2004) [Pubmed]
  16. Adrenomedullin receptor is found exclusively in noradrenaline-secreting cells of the rat adrenal medulla. Renshaw, D., Thomson, L.M., Michael, G.J., Carroll, M., Kapas, S., Hinson, J.P. J. Neurochem. (2000) [Pubmed]
  17. Differential expression of components of the cardiomyocyte adrenomedullin/intermedin receptor system following blood pressure reduction in nitric oxide-deficient hypertension. Zhao, Y., Bell, D., Smith, L.R., Zhao, L., Devine, A.B., McHenry, E.M., Nicholls, D.P., McDermott, B.J. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  18. Changes of adrenomedullin and receptor activity modifying protein 2 (RAMP2) in myocardium and aorta in rats with isoproterenol-induced myocardial ischemia. Qi, Y.F., Shi, Y.R., Bu, D.F., Pang, Y.Z., Tang, C.S. Peptides (2003) [Pubmed]
  19. Cardiomyopathy in streptozotocin-induced diabetes involves intra-axonal accumulation of calcitonin gene-related peptide and altered expression of its receptor in rats. Chottová Dvoráková, M., Kuncová, J., Pfeil, U., McGregor, G.P., Svíglerová, J., Slavíková, J., Kummer, W. Neuroscience (2005) [Pubmed]
  20. Alterations of intrarenal adrenomedullin and its receptor system in heart failure rats. Yoshihara, F., Nishikimi, T., Okano, I., Horio, T., Yutani, C., Matsuo, H., Takishita, S., Ohe, T., Kangawa, K. Hypertension (2001) [Pubmed]
  21. Alterations of adrenomedullin and its receptor system components in calcified vascular smooth muscle cells. Pan, C.S., Qi, Y.F., Wang, S.H., Zhao, J., Bu, D.F., Li, G.Z., Tang, C.S. Regul. Pept. (2004) [Pubmed]
  22. Anandamide-induced depressor effect in spontaneously hypertensive rats: role of the vanilloid receptor. Li, J., Kaminski, N.E., Wang, D.H. Hypertension (2003) [Pubmed]
  23. High-salt-induced increase in blood pressure: role of capsaicin-sensitive sensory nerves. Li, J., Wang, D.H. J. Hypertens. (2003) [Pubmed]
  24. Aspartate(69) of the calcitonin-like receptor is required for its functional expression together with receptor-activity-modifying proteins 1 and -2. Ittner, L.M., Luessi, F., Koller, D., Born, W., Fischer, J.A., Muff, R. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  25. Altered gene expression of adrenomedullin and its receptor system and molecular forms of tissue adrenomedullin in left ventricular hypertrophy induced by malignant hypertension. Tadokoro, K., Nishikimi, T., Mori, Y., Wang, X., Akimoto, K., Matsuoka, H. Regul. Pept. (2003) [Pubmed]
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