Calcimimetic and calcilytic drugs: just for parathyroid cells?
The cell surface calcium receptor (Ca2+ receptor) is a particularly difficult receptor to study because its primary physiological ligand, Ca2+, affects numerous biological processes both within and outside of cells. Because of this, distinguishing effects of extracellular Ca2+ mediated by the Ca2+ receptor from those mediated by other mechanisms is challenging. Certain pharmacological approaches, however, when combined with appropriate experimental designs, can be used to more confidently identify cellular responses regulated by the Ca2+ receptor and select those that might be targeted therapeutically. The Ca2+ receptor on parathyroid cells, because it is the primary mechanism regulating secretion of parathyroid hormone (PTH), is one such target. Calcimimetic compounds, which active this Ca2+ receptor and lower circulating levels of PTH, have been developed for treating hyperparathyroidism. The converse pharmaceutical approach, involving calcilytic compounds that block parathyroid cell Ca2+ receptors and stimulate PTH secretion thereby providing an anabolic therapy for osteoporosis, still awaits clinical validation. Although Ca2+ receptors are expressed throughout the body and in many tissues that are not intimately involved in systemic Ca2+ homeostasis, their physiological and/or pathological significance remains speculative and their value as therapeutic targets is unknown.
Nemeth
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NPS Pharmaceuticals, Inc., 30 College Street, Suite 301, Toronto, Ont., Canada. enemeth@npsp.com
D000814:Aniline Compounds / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D000069449:Cinacalcet; D005275:Fendiline / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006961:Hyperparathyroidism / Q000188:drug therapy; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology; D010024:Osteoporosis / Q000188:drug therapy; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism; D010627:Phenethylamines; D011437:Propylamines; D044169:Receptors, Calcium-Sensing / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013237:Stereoisomerism
D000814:Aniline Compounds; D015220:Calcium Channels; C107873:N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine; C436740:N-(2-hydroxy-3-(2-cyano-3-chlorophenoxy)propyl)-1,1-dimethyl-2-(2-nephthyl)ethylamine; C111654:NPS R-467; D009281:Naphthalenes; D010627:Phenethylamines; D011437:Propylamines; D044169:Receptors, Calcium-Sensing; D005275:Fendiline; D002118:Calcium; D000069449:Cinacalcet