Serpentine receptors for parathyroid hormone, calcitonin and extracellular calcium ions.

The cloning of the receptors for PTH, CT and extracellular calcium ions represents a significant advance in the elucidation of the mechanisms through which extracellular calcium ions are regulated. All are members of the superfamily of GPCR, and the inclusion of the Ca2+o-sensing receptor in this superfamily documents that extracellular calcium ions can serve as an extracellular first messenger, in addition to subserving their better known role as a key intracellular second messenger. Furthermore, it has proved possible to identify several human diseases that result from inactivating or activating mutations in the PTH or Ca2+o-sensing receptor. Finally, the availability of these cloned receptors will enable many more studies on structure-function relationships for these receptors as well as clarifying their tissue distribution, regulation and roles in health and disease. It may also be possible to design novel therapeutic agents that permit manipulation of the receptors when their function is abnormal.