Structural, genetic and pharmacological identity of the rat alpha 2-adrenergic receptor subtype cA2-47 and its molecular characterization in rat adrenal, adrenocortical carcinoma and bovine retina.

Subsequent to the first alpha 2-adrenergic receptor (alpha 2-AR) gene cloning of alpha 2-C10 from human platelet, cloning of the first rodent alpha 2-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 alpha 2A-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 Thus, the precise structural comparison of the rat receptor to the human platelet receptor is no longer valid.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 alpha 2-AR gene, RG20, was then cloned and was also found to be a structural analog of the human alpha 2-C10. It, however, varied slightly from the alpha 2A subtype pharmacology, but matched the newly defined alpha 2D subtype pharmacology. It was, therefore, concluded that RG20 encodes the alpha 2D 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 alpha 2D 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 alpha 2-C10 receptor, and also the localization of cA2-47 transcript in certain rat tissues. The results show that the cA2-47 receptor shows a high degree of sequence identity to the alpha 2-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 alpha 2D 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.