Identification of an orphan receptor gene as a type 1 calcitonin gene-related peptide receptor.
Calcitonin gene-related peptide (CGRP) is a 37 residue neuropeptide that is distantly related to adrenomedullin. We have recently reported the cloning and expression of an adrenomedullin receptor which is approximately 30% homologous to the canine orphan receptor RDC-1. Therefore we tested the hypothesis that RDC-1 was a CGRP receptor. The RDC-1 gene was expressed in COS-7 cells and showed a dose dependant increase of cAMP in response to CGRP and adrenomedullin (EC50 values of 3 x 10(-9) M and 1 x 10(-7) M respectively) which was inhibited by the CGRP antagonist CGRP[8-37]. There was no cAMP response to amylin or [Cys(acm)2,7]a-hCGRP. Ligand binding studies confirmed high affinity of this receptor for CGRP and CGRP[8-37] with KD values of 9.2 x 10(-9) M and 13.4 x 10(-9) M respectively.
Kapas
S
S
Department of Chemical Endocrinology, Medical College of St Bartholomew's Hospital, London, U.K.
Clark
A J
AJ
D053607:Adrenomedullin; D000818:Animals; D001483:Base Sequence; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D004285:Dogs; D015870:Gene Expression; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D058265:Receptors, Adrenomedullin; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018000:Receptors, Peptide; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014162:Transfection
D017931:DNA Primers; D018076:DNA, Complementary; D008565:Membrane Proteins; D010455:Peptides; D012333:RNA, Messenger; D058265:Receptors, Adrenomedullin; D018015:Receptors, Calcitonin Gene-Related Peptide; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; D053607:Adrenomedullin; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide