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Structural, genetic and pharmacological identity of the rat α2-adrenergic receptor subtype cA2-47 and its molecular characterization in rat adrenal, adrenocortical carcinoma and bovine retina

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Abstract

Subsequent to the first α2-adrenergic receptor (α2-AR) gene cloning of α2-C10 from human platelet, cloning of the first rodent α2-AR cDNA, cA2-47, was reported. Based on the structural and limited pharmacological comparison, it was concluded that the rodent receptor is a molecular and pharmacological analog of the human receptor, which is pharmacologically classified as the α2A-AR. A later study slightly revised the structure of the human receptor. Thus, the precise structural comparison of the rat receptor to the human platelet receptor is no longer valid. Another rat α2-AR gene, RG20, was then cloned and was also found to be a structural analog of the human α2-C10. It, however, varied slightly from the α2A subtype pharmacology, but matched the newly defined α2D subtype pharmacology. It was, therefore, concluded that RG20 encodes the α2D subtype. The structural and pharmacological relationship of RG20 with cA2-47 is not known, although it has been tacitly assumed that both are the identical α2D receptor subtypes. The present study addresses this and other issues relating to the precise structural, genetic and pharmacological relationship of cA2-47 with the human platelet α2-C10 receptor, and also the localization of cA2-47 transcipt in certain rat tissues. The results show that the cA2-47 receptor shows a high degree of sequence identity to the α2-C10 receptor, yet important differences exist between them. The sequence identity of cA2-47 receptor to the RG20 receptor is almost, but not quite complete. The cA2-47 gene is not present in the human and the human gene is not present in the rat; that cA2-47 receptor subtype is pharmacologically similar to the RG20 receptor subtype, both being of the α2D subtype. The cA2-47 receptor transcript in addition to being found in the rat brain is present in the rat adrenal gland, testes, adrenocortical carcinoma and the bovine retina.

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Wypijewski, K., Duda, T. & Sharma, R.K. Structural, genetic and pharmacological identity of the rat α2-adrenergic receptor subtype cA2-47 and its molecular characterization in rat adrenal, adrenocortical carcinoma and bovine retina. Mol Cell Biochem 144, 181–190 (1995). https://doi.org/10.1007/BF00944398

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