Heterogeneity of the calcitonin receptor: Functional aspects in osteoclasts and other sites

The recent cloning of the calcitonin receptor reveals it as a member of a new family of 7-transmembrane, G protein-linked receptors. Data from rat, mouse and human receptor cloning reveal that in each of these species the receptor exists in more than one form, most likely the result of alternate splicing. In the rat, the two forms are C1a and C1b, the latter differing from C1a in that it contains a 37-amino acid insert in the second extracellular domain. The two receptor isoforms differ in their distribution in vivo, with the C1b predominantly in the central nervous system and C1a in other tissues. Both forms have been shown to be present in mature and developing osteoclasts, with the C1a isoform predominating. The two isoforms differ in their kinetics and pharmacological properties, with C1b being virtually unable to bind the human and rat calcitonins but readily binding salmon calcitonin. It will be important to elucidate the physiological significance of the structural heterogeneity of the calcitonin receptor.