A cDNA encoding the calcitonin gene-related peptide type 1 receptor.
Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse biological effects including potent vasodilator activity. We report here the cloning of a complementary DNA (cDNA) encoding a human CGRP1 receptor, which shares significant peptide sequence homology with the human calcitonin receptor, a member of the G-protein-coupled receptor superfamily. Northern blot analysis revealed that the messenger RNA for this receptor is predominantly expressed in the lung and heart. In situ studies showed specific localization of the receptor mRNA to alveolar cells in the lung and to cardiac myocytes in the heart. Stable expression of the cDNA in human embryonic kidney 293 (HEK 293) cells produced specific, high affinity binding sites for CGRP that displayed pharmacological and functional properties very similar to native human CGRP1 receptor. Exposure of these cells to CGRP resulted in a 60-fold increase in cAMP production, which was inhibited in a competitive manner by the CGRP1 receptor antagonist, CGRP-(8-37).
Aiyar
N
N
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
Rand
K
K
Elshourbagy
N A
NA
Zeng
Z
Z
Adamou
J E
JE
Bergsma
D J
DJ
Li
Y
Y
D053607:Adrenomedullin; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D015152:Blotting, Northern; D002116:Calcitonin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney; D008168:Lung / Q000378:metabolism; D008322:Mammals; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D016324:Sequence Tagged Sites; D014162:Transfection
D017931:DNA Primers; D018076:DNA, Complementary; D010455:Peptides; D018015:Receptors, Calcitonin Gene-Related Peptide; D011994:Recombinant Proteins; D053607:Adrenomedullin; D002116:Calcitonin; D019204:GTP-Binding Proteins; D015740:Calcitonin Gene-Related Peptide