Abstract
Two major rat calcitonin receptor isoforms CT(a) and CT(b) have been described in rat brain with an overlapping distribution pattern particularly in hypothalamic regions. Generated by alternative splicing CT(a) and CT(b) differ in their second extracellular domain and display altered ligand binding kinetics for calcitonin, amylin and CGRP in vitro. To better understand their functional roles in vivo we examined CT(a) and CT(b) expression in peptidergic neurons of the lateral hypothalamic area (LHA) using isoform-specific probes and primers in double in situ hybridization experiments and RT-PCR analysis of laser microdissected cellular RNA extracts. We found the CT(b) isoform exclusively expressed in all orexin neurons of the LHA indicating that CT related neuropeptides may directly modulate the activity of orexin neurons. An as yet unidentified magnocellular neuronal population expressed CT(a) mRNA. Interestingly, MCH neurons lack expression of both CT receptor isoforms. The cell-specific distribution pattern in the LHA strongly suggest an isoform-selective role of CT receptors in the neuroendocrine regulation of eating and body weight regulation and of sleep.
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