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

• Quantification of gene transcripts revealed expression of all RAMP isoforms and CRLR in cultured rat vascular smooth muscle cells (VSMCs), RAMP2 and RAMP3 in rat endothelial cells, and RAMP1 in rat fibroblasts [9].
• CRLR expression was minimal in endothelial cells and fibroblasts [9].
• 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 [13].
• The expression of mRNA for calcitonin receptor-like receptor/receptor-activity modifying proteins in rat peritoneal mast cells [14].
• Our results demonstrate that CGRP, CRLR, RAMP1 and RAMP2 exist in the nucleus accumbens of intact rats, and that they were significantly upregulated in rats with inflammation [15].

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

• Recently, a novel adrenomedullin receptor has been identified as a complex of calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein 2 (RAMP2) [18].
• Calcitonin gene-related peptide (CGRP) is a vasorelaxant and positive inotropic and chronotropic peptide that binds to the calcitonin receptor-like receptor [19].
• Calcitonin receptor-like receptor/receptor activity-modifying protein 2 (CRLR/RAMP2) and CRLR/RAMP3 complexes have been reported to be specific adrenomedullin (AM) receptors [20].

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

• RT-PCR and northern blot analysis revealed greater abundance of mRNA for L1 than for CRLR, possibly suggesting that L1 may be the major adrenomedullin receptor expressed in this tissue [16].
• Expression of components of the CGRP receptor, calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1), was determined by the use of Western blot analysis [23].
• Conversely, cardiac expression of calcitonin receptor-like receptor initially (4 weeks after treatment) increased but then gradually declined to 47% of control levels in both atria after 16 weeks [19].
• Co-immunoprecipitation of RAMP1 with the CLR, indicating complex formation, was reduced with the D69A, D69N, and D69E mutants [24].
• Gene expression of AM was measured by Northern blot analysis and gene expression of AM receptor system components, such as calcitonin receptor-like receptor (CRLR), receptor activity modifying protein 2 (RAMP2), and RAMP3 was measured by the reverse transcription polymerase chain reaction method [25].

References