Cloning, characterization and central nervous system distribution of receptor activity modifying proteins in the rat

• DOI: 10.1046/j.0953-816x.2001.01688.x
• Publication Date: 2003-03-06T14:42:03Z
• Authors: K. R. Oliver; S. A. Kane; C. A. Salvatore; J. J. Mallee; A. M. Kinsey; K. S. Koblan; N. Keyvan‐Fouladi; R. P. Heavens; A. Wainwright; M. Jacobson; I. M. Dickerson; R. G. Hill
• Keywords: Amylin; Calcitonin receptor; Adrenomedullin

Calcitonin gene-related peptide (CGRP), adrenomedullin (ADM), amylin and calcitonin (CT) are structurally functionally related neuropeptides. It has recently been shown that the molecular pharmacology of CGRP ADM is determined by coexpression one three receptor activity-modifying proteins (RAMPs) with receptor-like (CRLR). Furthermore, RAMP have also to govern receptor, which in association RAMP1 or RAMP3, binds high affinity. In this study, we cloned rat family characterized receptors. Rat RAMP1, RAMP2 RAMP3 shared 72%, 69% 85% homology their respective human homologues. As expected CRLR-RAMP1 conferred sensitivity CGRP, whilst CRLR affinity binding. Using specific oligonucleotides expression mRNAs central nervous system situ hybridization. The localization was heterogeneous. mRNA predominantly expressed cortex, caudate putamen olfactory tubercles; most abundant hypothalamus; restrictively thalamic nuclei. Interestingly, brain areas only a single often detected, suggesting mutual exclusivity expression. These data allow predictions be made where each protein may heterodimerize its partner G-protein-coupled receptor(s) at cellular level consequently advance current understanding sites action ADM, CT. these suggest associate modify behaviour other, as yet unidentified neurotransmitter