IDENTIFICATION OF BRAIN ISOFORMS OF THE RAT CALCITONIN RECEPTOR

Two rat calcitonin receptor isoforms have been identified by cDNA clon ing from a hypothalamic library. The clones, C1a and C1b, specified pr oteins of 478 and 515 amino acids, respectively. The clones were ident ical, except that the C1b sequence encoded a 37-amino acid insert in t he second extracellular domain, which conferred altered ligand recogni tion. Compared to the C1a receptor, expressed C1b receptors exhibited decreased affinity for porcine CT, relative to salmon CT, and negligib le affinity for human CT. Clone C1b mRNA was predominately expressed i n the brain, whereas mRNA for the C1a clone was present in both brain and peripheral tissues. Both receptors were able to couple functionall y to adenylate cyclase. Thus, clone C1b represents a novel brain isofo rm of the CT receptor with different affinity for CT analogs resulting from an altered second extracellular domain.