Comparative affinities of human adrenomedullin for 125I-labelled human alpha calcitonin gene related peptide ([125I]hCGRP alpha) and 125I-labelled Bolton-Hunter rat amylin ([125I]BHrAMY) specific binding sites in the rat brain.
Adrenomedullin (ADM) is a recently identified peptide that shows some homology (approximately 25%) with calcitonin gene related peptide (CGRP) and is now considered to be a new member of this peptide family. Because it shares biological effects with CGRP, we evaluated the possible affinity of human adrenomedullin (hADM) for 125I-labelled human CGRP alpha ([125I]hCGRP alpha) binding sites in the rat brain. Moreover, we evaluated the potential existence of cross-reactivity for 125I-labelled Bolton-Hunter rat amylin ([125I]BHrAMY), another member of this peptide family. In all brain areas investigated, hADM only competed with relatively low affinities for both [125I]hCGRP alpha and [125I]BHrAMY binding sites, with IC50 values generally in the high nanomolar-low micromolar range, the lowest affinity being observed for [125I]BHrAMY binding sites. Interestingly, the lowest affinities of hADM against both radioligands were detected in the nucleus accumbens and ventral striatum. These areas are known to be enriched with atypical CGRP - salmon calcitonin - amylin sensitive sites. It thus appears that hADM is unlikely to bind to this atypical site. Moreover, hADM demonstrated limited affinity for either [125I]hCGRP alpha or [125I]BHrAMY binding sites in the rat brain. This suggests that the potential biological effects of ADM in the brain could be mediated through a different class of receptors with higher affinity for this newly isolated peptide.
van Rossum
D
D
Douglas Hospital Research Center, Verdun, QC, Canada.
Ménard
D P
DP
Chang
J K
JK
Quirion
R
R
D053607:Adrenomedullin; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism*; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D006801:Humans; D008297:Male; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism*; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide / Q000378:metabolism*
D000959:Antihypertensive Agents; D010455:Peptides; D018015:Receptors, Calcitonin Gene-Related Peptide; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide; D053607:Adrenomedullin