Calcitonin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

This receptor family comprises a group of receptors for the calcitonin/CGRP family of peptides. The calcitonin (CT), amylin (AMY), calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on CGRP, AM, AMY, and CT receptors [122, 67]) are generated by the genes CALCR (which codes for the CT receptor) and CALCRL (which codes for the calcitonin receptor-like receptor, CLR, previously known as CRLR). Their function and pharmacology are altered in the presence of RAMPs (receptor activity-modifying proteins), which are single TM domain proteins of ca. 130 amino acids, identified as a family of three members; RAMP1, RAMP2 and RAMP3. There are splice variants of the CT receptor; these in turn produce variants of the AMY receptor [122], some of which can be potently activated by CGRP. The endogenous agonists are the peptides calcitonin, α-CGRP (formerly known as CGRP-I), β-CGRP (formerly known as CGRP-II), amylin (occasionally called islet-amyloid polypeptide, diabetes-associated polypeptide), adrenomedullin and adrenomedullin 2/intermedin. There are species differences in peptide sequences, particularly for the CTs. CTR-stimulating peptide (CRSP) is another member of the family with selectivity for the CT receptor but it is not expressed in humans [87]. olcegepant (also known as BIBN4096BS, pKi~10.5) and telcagepant (also known as MK0974, pKi~9) are the most selective antagonists available, showing selectivity for CGRP receptors, with a particular preference for those of primate origin. CLR (calcitonin receptor-like receptor) by itself binds no known endogenous ligand, but in the presence of RAMPs it gives receptors for CGRP, adrenomedullin and adrenomedullin 2/intermedin

Catalysis and evolution on cycling of nano-structured magnesium multilayer thin films

This paper explores the hydrogen cycling properties of Mg/Cr and Mg/V multilayer thin films and studies the effect of chromium and vanadium transition metal catalysts on the cycling properties of thick magnesium coatings. Two transition-metal catalysed magnesium-based multilayer PVD coatings are compared with a non-catalysed magnesium control sample. The (micro-)structural evolution of the thin film coatings into fine, flakey powders is studied in depth using XRD, SEM and TEM and the hydrogen storage properties of all three materials are assessed using volumetric, gravimetric and calorimetric methods focussing on the effect of the microstructure and composition of the coatings on the hydrogen storage kinetics. It was found that the chromiumcatalysed coating had the most favourable hydrogen storage kinetics with an activation energy for the dehydrogenation reaction of 65.7±2.5 kJ mol-1 and a hydrogen capacity of 6.1±0.3 wt%. The mechanism of the dehydrogenation reaction of the catalysed samples was studied using the CV and JMAK kinetic models and it was found that the catalyst material influenced not only the hydrogen storage kinetics but also the mechanism of the reaction

Calcitonin receptors in GtoPdb v.2023.1

This receptor family comprises a group of receptors for the calcitonin/CGRP family of peptides. The calcitonin (CT), amylin (AMY), calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on CGRP, AM, AMY, and CT receptors [131, 74, 71]) are generated by the genes CALCR (which codes for the CT receptor, CTR) and CALCRL (which codes for the calcitonin receptor-like receptor, CLR, previously known as CRLR). Their function and pharmacology are altered in the presence of RAMPs (receptor activity-modifying proteins), which are single TM domain proteins of ca. 150 amino acids, identified as a family of three members; RAMP1, RAMP2 and RAMP3. There are splice variants of the CTR; these in turn produce variants of AMY receptors [131], some of which can be potently activated by CGRP. The endogenous agonists are the peptides calcitonin, α-CGRP (formerly known as CGRP-I), β-CGRP (formerly known as CGRP-II), amylin (occasionally called islet-amyloid polypeptide, diabetes-associated polypeptide), adrenomedullin and adrenomedullin 2/intermedin. There are species differences in peptide sequences, particularly for the CTs. CTR-stimulating peptide (CRSP) is another member of the family with selectivity for the CTR but it is not expressed in humans [93]. CLR (calcitonin receptor-like receptor) by itself binds no known endogenous ligand, but in the presence of RAMPs it gives receptors for CGRP, adrenomedullin and adrenomedullin 2/intermedin. There are several approved drugs that target this receptor family, such as pramlintide, erenumab, and the "gepant" class of CGRP receptor antagonists. There are also species differences in agonist pharmacology; for example, CGRP displays potent activity at multiple rat and mouse receptors [58, 15]. The summary table only reflects human receptor pharmacology

Absence of force suppression in rabbit bladder correlates with low expression of heat shock protein 20

BACKGROUND: Nitroglycerin can induce relaxation of swine carotid artery without sustained reductions in [Ca(2+)](i )or myosin regulatory light chain (MRLC) phosphorylation. This has been termed force suppression and been found to correlate with ser(16)-phosphorylation of heat shock protein 20 (HSP20). We tested for the existence of this mechanism in a smooth muscle that is not responsive to nitric oxide. METHODS: Isometrically mounted mucosa free rabbit bladder strips were contracted with carbachol and relaxed with 8-Br-cGMP, forskolin, or isoprenaline. RESULTS: Contraction was associated with a highly cooperative relation between MRLC phosphorylation and force such that very small increases in MRLC phosphorylation induced large increases in force. Relaxation induced by 8-Br-cGMP, forskolin, or isoprenaline did not shift the MRLC phosphorylation-force relation from that observed with carbachol alone, i.e. there was no force suppression. HSP20 content was negligible (approximately two hundred-fold less than swine carotid). CONCLUSION: The lack of force suppression in the absence of HSP20 is consistent with the hypothesized role for HSP20 in the force suppression observed in tonic smooth muscles

'The difference in determinants of Chlamydia trachomatis and Mycoplasma genitalium in a sample of young Australian women.'

BACKGROUND Differences in the determinants of Chlamydia trachomatis ('chlamydia') and Mycoplasma genitalium (MG) genital infection in women are not well understood. METHODS A cohort study of 16 to 25 year old Australian women recruited from primary health care clinics, aimed to determine chlamydia and MG prevalence and incidence. Vaginal swabs collected at recruitment were used to measure chlamydia and MG prevalence, organism-load and chlamydia-serovar a cross-sectional analysis undertaken on the baseline results is presented here. RESULTS Of 1116 participants, chlamydia prevalence was 4.9% (95% CI: 2.9, 7.0) (n = 55) and MG prevalence was 2.4% (95% CI: 1.5, 3.3) (n = 27). Differences in the determinants were found - chlamydia not MG, was associated with younger age [AOR:0.9 (95% CI: 0.8, 1.0)] and recent antibiotic use [AOR:0.4 (95% CI: 0.2, 1.0)], and MG not chlamydia was associated with symptoms [AOR:2.1 (95% CI: 1.1, 4.0)]. Having two or more partners in last 12 months was more strongly associated with chlamydia [AOR:6.4 (95% CI: 3.6, 11.3)] than MG [AOR:2.2 (95% CI: 1.0, 4.6)] but unprotected sex with three or more partners was less strongly associated with chlamydia [AOR:3.1 (95%CI: 1.0, 9.5)] than MG [AOR:16.6 (95%CI: 2.0, 138.0)]. Median organism load for MG was 100 times lower (5.7 × 104/swab) than chlamydia (5.6 × 10⁶/swab) (p < 0.01) and not associated with age or symptoms for chlamydia or MG. CONCLUSIONS These results demonstrate significant chlamydia and MG prevalence in Australian women, and suggest that the differences in strengths of association between numbers of sexual partners and unprotected sex and chlamydia and MG might be due to differences in the transmission dynamics between these infections.This project was funded by the Commonwealth of Australia, as part of a National Chlamydia Pilot program that is currently running to test the effectiveness of a number of models for chlamydia testing in Australia. This project will assist in developing possible recommendations for a National Chlamydia Program. The analysis of MG was funded by the National Health and Research Council (research grant number 509144)