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

Autor:	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
Rok vydání:	2001
Předmět:	Calcitonin Central Nervous System Male Telencephalon Amyloid DNA Complementary Calcitonin Gene-Related Peptide Molecular Sequence Data Receptor Activity-Modifying Protein 2 Receptor Activity-Modifying Protein 3 Receptor Activity-Modifying Proteins Receptor Activity-Modifying Protein 1 Rats Sprague-Dawley Adrenomedullin Mesencephalon Animals Amino Acid Sequence RNA Messenger Cloning Molecular Diencephalon Cells Cultured Sequence Homology Amino Acid Calcitonin Receptor-Like Protein Neuropeptides Intracellular Signaling Peptides and Proteins Membrane Proteins Receptors Calcitonin Islet Amyloid Polypeptide Rats Rhombencephalon Spinal Cord Peptides
Zdroj:	The European journal of neuroscience. 14(4)
ISSN:	0953-816X
Popis:	Calcitonin gene-related peptide (CGRP), adrenomedullin (ADM), amylin and calcitonin (CT) are structurally and functionally related neuropeptides. It has recently been shown that the molecular pharmacology of CGRP and ADM is determined by coexpression of one of three receptor activity-modifying proteins (RAMPs) with calcitonin receptor-like receptor (CRLR). Furthermore, RAMP proteins have also been shown to govern the pharmacology of the calcitonin receptor, which in association with RAMP1 or RAMP3, binds amylin with high affinity. In this study, we have cloned the rat RAMP family and characterized the pharmacology of rat CGRP and ADM receptors. Rat RAMP1, RAMP2 and RAMP3 shared 72%, 69% and 85% homology with their respective human homologues. As expected CRLR-RAMP1 coexpression conferred sensitivity to CGRP, whilst association of RAMP2 or RAMP3 with CRLR conferred high affinity ADM binding. Using specific oligonucleotides we have determined the expression of RAMP1, RAMP2 and RAMP3 mRNAs in the rat central nervous system by in situ hybridization. The localization of RAMP mRNAs was heterogeneous. RAMP1 mRNA was predominantly expressed in cortex, caudate putamen and olfactory tubercles; RAMP2 mRNA was most abundant in hypothalamus; and RAMP3 was restrictively expressed in thalamic nuclei. Interestingly, in specific brain areas only a single RAMP mRNA was often detected, suggesting mutual exclusivity in expression. These data allow predictions to be made of where each RAMP protein may heterodimerize with its partner G-protein-coupled receptor(s) at the cellular level and consequently advance current understanding of cellular sites of action of CGRP, ADM, amylin and CT. Furthermore, these localization data suggest that the RAMP family may associate and modify the behaviour of other, as yet unidentified neurotransmitter receptors.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::4849b4cc6632099ff306ed9f0c333d5f https://pubmed.ncbi.nlm.nih.gov/11556887 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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