title: [Pharmacological characteristics of drugs targeted on calcium-sensing receptor.-properties of cinacalcet hydrochloride as allosteric modulator].
abstract: Calcimimetics act as positive allosteric modulators of the calcium-sensing receptor (CaSR), thereby decreasing parathyroid hormone (PTH) secretion from the parathyroid glands. On the other hand, negative allosteric modulators of the CaSR with stimulatory effect on PTH secretion are termed calcilytics. The calcimimetic cinacalcet hydrochloride (cinacalcet) is the world's first allosteric modulator of G protein-coupled receptor to enter the clinical market. Cinacalcet just tunes the physiological effects of Ca(2+), an endogenous ligand, therefore, shows high selectivity and low side effects. Calcimimetics also increase cell surface CaSR expression by acting as pharmacological chaperones (pharmacoperones). It is considered that the cinacalcet-induced upper gastrointestinal problems are resulted from enhanced physiological responses to Ca(2+) and amino acids via increased sensitivity of digestive tract CaSR by cinacalcet. While clinical developments of calcilytics for osteoporosis were unfortunately halted or terminated due to paucity of efficacy, it is expected that calcilytics may be useful for the treatment of patients with activating CaSR mutations, asthma, and idiopathic pulmonary artery hypertension.
authors.affiliation: Kidney Disease and Dialysis Center, Hidaka-kai, Takasaki, Gunma, Japan/Department of Medicine, Medical Center East, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Nagano
authors.affiliation: Kidney Disease and Dialysis Center, Hidaka-kai, Takasaki, Gunma, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Tsutsui
mesh_terms: D000494:Allosteric Regulation; D040761:Biomimetic Materials / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000069449:Cinacalcet / Q000494:pharmacology*; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D011485:Protein Binding; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*
chemical_list: D018832:Molecular Chaperones; D044169:Receptors, Calcium-Sensing; D002118:Calcium; D000069449:Cinacalcet