TY - JOUR
T1 - Molecular cloning and expression of the cDNA for the α(1A)-adrenergic receptor
T2 - The gene for which is located on human chromosome 5
AU - Lomasney, Jon W.
AU - Cotecchia, Susanna
AU - Lorenz, Wulfing
AU - Leung, Wah Ying
AU - Schwinn, Debra A.
AU - Yang-Feng, Teresa L.
AU - Brownstein, Michael
AU - Lefkowitz, Robert J.
AU - Caron, Marc G.
PY - 1991
Y1 - 1991
N2 - Pharmacological and molecular cloning studies have demonstrated heterogeneity of α1-adrenergic receptors. We have now cloned two α1-adrenergic receptors from a rat cerebral cortex cDNA library, using the hamster α(1B)-adrenergic receptor as a probe. The deduced amino acid sequence of clone RA42 encodes a protein of 560 amino acids whose putative topology is similar to that of the family of G-protein-coupled receptors. The primary structure though most closely resembles that of an α1-adrenergic receptor, having approximately 73% amino acid identity in the putative transmembrane domains with the previously isolated hamster α(1B) receptor. Analysis of the ligand binding properties of RA42 expressed in COS-7 cells with a variety of adrenergic ligands demonstrates a unique α1-adrenergic receptor pharmacology. High affinity for the antagonist WB4101 and agonists phenylephrine and methoxamine suggests that cDNA RA42 encodes the α(1A) receptor subtype. Northern blot analysis of various rat tissues also shows the distribution expected of the α(1A) receptor subtype with abundant expression in vas deferens followed by hippocampus, cerebral cortex, aorta, brainstem, heart and spleen. The second α1-adrenergic receptor cloned represents the rat homolog of the hamster α(1B) subtype. Expression of mRNA for this receptor is strongly detected in liver followed by heart, cerebral cortex, brain stem, kidney, lung, and spleen. This study provides definitive evidence for the existence of three α1-adrenergic receptor subtypes.
AB - Pharmacological and molecular cloning studies have demonstrated heterogeneity of α1-adrenergic receptors. We have now cloned two α1-adrenergic receptors from a rat cerebral cortex cDNA library, using the hamster α(1B)-adrenergic receptor as a probe. The deduced amino acid sequence of clone RA42 encodes a protein of 560 amino acids whose putative topology is similar to that of the family of G-protein-coupled receptors. The primary structure though most closely resembles that of an α1-adrenergic receptor, having approximately 73% amino acid identity in the putative transmembrane domains with the previously isolated hamster α(1B) receptor. Analysis of the ligand binding properties of RA42 expressed in COS-7 cells with a variety of adrenergic ligands demonstrates a unique α1-adrenergic receptor pharmacology. High affinity for the antagonist WB4101 and agonists phenylephrine and methoxamine suggests that cDNA RA42 encodes the α(1A) receptor subtype. Northern blot analysis of various rat tissues also shows the distribution expected of the α(1A) receptor subtype with abundant expression in vas deferens followed by hippocampus, cerebral cortex, aorta, brainstem, heart and spleen. The second α1-adrenergic receptor cloned represents the rat homolog of the hamster α(1B) subtype. Expression of mRNA for this receptor is strongly detected in liver followed by heart, cerebral cortex, brain stem, kidney, lung, and spleen. This study provides definitive evidence for the existence of three α1-adrenergic receptor subtypes.
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M3 - Article
C2 - 1706716
AN - SCOPUS:0025822139
VL - 266
SP - 6365
EP - 6369
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 10
ER -