Vascular alpha-adrenoceptors: from the gene to the human

Canadian Journal of Physiology and Pharmacology
D B BylundR R Ruffolo


Adrenoceptors can be subdivided into three major types, the alpha 1-, alpha 2-, and beta-adrenoceptors. Each of these types can be further subdivided into three subtypes, based on pharmacological characteristics. Molecular cloning techniques have supported this subclassification. Recent data now suggest that alpha-adrenoceptor subtypes identified by pharmacological and molecular techniques correspond well, although species orthologs of several adrenoceptor subtypes have been identified. The secondary structure of the adrenoceptors has been elucidated and correlated with their interaction with second messenger molecules. alpha 1-Adrenoceptors, beta-adrenoceptors, and alpha 2-adrenoceptors mediate their actions through stimulation of inositol phosphate release, stimulation of adenylate cyclase, and inhibition of adenylate cyclase, respectively. Site-directed mutagenesis and the preparation of chimeric receptors have located the site of receptor--second messenger interaction to the third intracellular loop for each of these adrenoceptors. While subtypes of each of these classes all interact with the same second messenger, studies with recombinant alpha 2-adrenoceptors show subtype-related differences in receptor--second messenger ...Continue Reading


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