Disease relevance of Calcr

• TGF-beta 1 strongly inhibited the generation of calcitonin receptor (CTR)-positive cells in mouse bone marrow cultures, but as for isolated osteoclasts, bone resorption per CTR-positive cell was increased [1].

High impact information on Calcr

• Autoradiographic evidence for a calcitonin receptor on testicular Leydig cells [2].
• Furthermore, it was found that alpha C1A-C1B bound to a peptide containing the C2 domain of PKC alpha [3].
• The alpha C1A-C1B domain also activated conventional PKC beta I, -beta II, and -gamma isoforms, but not novel PKC delta or -epsilon [3].
• CONCLUSION: Focal bone erosion in CIA is attributed to cells expressing definitive features of osteoclasts, including CTR [4].
• TRAP-positive multinucleated cells were detected within synovium and at the bone erosive front; however, CTR-positive multinucleated cells were present only at sites adjacent to bone [4].

Chemical compound and disease context of Calcr

• Following a 20-day period, locally released PGE2 at doses of 0.1 and 0.05 mg/day appears to affect alveolar bone resorption in the periodontium of rats, as the number of multinucleated cells expressing TRAP and CTR are significantly reduced [5].

Biological context of Calcr

• Our current study also explored the relationship between the expression of CTR isoforms and amylin binding sites [6].
• In conclusion, we suggest that adrenomedullin in the rat cranial circulation dilates dural and pial arteries, reduces mean arterial blood pressure and increases LCBF(Flux), probably via a CGRP1-receptor [7].
• Levels of mRNAs for pit-CT, CT receptor, prolactin (PRL), and beta-LH during 4-d estrous cycle were determined [8].
• Direct sequence of RT-PCR products for CTR showed no different nucleotide sequences between the two strains [9].
• However, hypocalcemic activity, calcitonin-receptor binding activity and the biodistribution of the derivatives were affected by the glycosylation and were dependent on both the carbohydrate structure and the glycosylation site [10].

Anatomical context of Calcr

• CONCLUSIONS: CTR C1a protein expression has been identified in the ureteric ducts in the metanephros and both isoforms expressed in the distal portions of the developing nephrons and collecting ducts [6].
• RESULTS: The CTR C1a isoform is expressed in the ureteric ducts of the metanephros and both isoforms are expressed in the developing distal convoluted tubules, ascending limbs of the loop of Henle and collecting ducts in the postnatal rat kidney [6].
• Ontogeny of calcitonin receptor mRNA and protein in the developing central nervous system of the rat [11].
• However, we detected CTR immunoreactivity in several additional brain areas, as the ventromedial, lateral and posterior hypothalamus, where CT binding has not yet been described [12].
• Then, porcine RAMPs, CRLR and CTR were expressed in COS-7 or porcine vascular smooth muscle cells, and the resulting receptor complexes were analyzed by the cyclic adenosine 3,5-monophosphate (cAMP) production assay [13].

Associations of Calcr with chemical compounds

• Based on these findings, it is proposed that the activating conformational change in PKC alpha results from the dissociation of intra-molecular interactions between the alpha C1A-C1B domain and the C2 domain [3].
• The minimal chain length required to activate adenylate cyclase in rat renal plasma membranes was between 12-18 amino acids, and the minimal chain length required to affect the CT receptor binding was between 6-12 amino acids, near the C-terminus [14].
• In cocultures of clonal marrow stromal cells (MS1) and normal mouse spleen cells, both 1,25-dihydroxyvitamin D3 and rat PTH (rPTH)-(1-34) can induce the formation of tartrate-resistant acid phosphatase- and calcitonin receptor-positive multinucleated osteoclast-like cells, which can attach to dentine slices and produce resorption pits [15].
• Pretreatment of hyperglycemic rats with the CT synthesis inhibitor metyrapone or the CT receptor antagonist, RU38486, prevents hyperglycemic aggravation of ischemic neuronal damage [16].
• Autoradiography of polyacrylamide gels of cross-linked calcitonin receptor showed only three protein bands specifically binding salmon calcitonin [17].

Physical interactions of Calcr

• Calcitonin receptor binding sites were identified in renal cortex and medulla using the radioligand 125I-salmon calcitonin [18].

Regulatory relationships of Calcr

• Peripheral amylin activates circumventricular organs expressing calcitonin receptor a/b subtypes and receptor-activity modifying proteins in the rat [19].
• Heterologous desensitization was also seen, as manifested by decreased calcitonin (CT)-stimulated adenylate cyclase activity with normal CT receptor binding [20].

Other interactions of Calcr

• In this study, the expression of receptors for calcitonin (CTR), the CTR C1a and C1b isoforms, was investigated during development of the fetal rat central nervous system (CNS) by using in situ hybridization and immunohistochemistry [11].
• Using an in vitro assay containing only purified recombinant proteins and the phorbol ester, 4 beta-12-O-tetradecanoylphorbol-13-acetate (TPA), but lacking lipids, it was found that PKC alpha bound specifically, and with high affinity, to a alpha C1A-C1B fusion protein of the same isozyme [3].
• Moreover, low IL-15 concentration (0.1 ng/ml) strongly increased the level of calcitonin receptor mRNA of mononuclear preosteoclast-like cells [21].
• The double detection of these two antigen molecules with osteoclast-specific antigen and with calcitonin receptor, using a fluorescence-activated cell sorter or autoradiography technique, revealed that LFA-1 and ICAM-1 were expressed on the preosteoclasts [22].

Analytical, diagnostic and therapeutic context of Calcr

• In vitro autoradiography demonstrated that while amylin binding sites were predominantly in the cortex, CTR expression was largely localized in the medulla in an earlier event, followed by cortical expression [6].
• Calcitonin receptors (CTR) have previously been identified in specific regions of the rat central nervous system using in situ hybridization or autoradiography with iodinated ligands [12].
• In this study, the results of immunohistochemical mapping of CTR in the adult rat brain are reported, using a potent and recently developed antibody that recognizes an intracellular epitope of the rat CTR, and high-resolution immunofluorescence techniques [12].
• Both the C1a and C1b CT receptor isoforms were present in the cultures, as assessed by RT-PCR [23].
• We demonstrated that both Wistar and WAG/Rij rats expressed type-C1a CTR by RT-PCR analysis and their mRNA expressions were approximately equal by Northern blotting analysis [9].

References