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DT Price, RS Chari, DE Berkowitz, WC Meyers and DA Schwinn
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.
At least three subtypes of alpha 1-adrenergic receptors (alpha 1ARs) have been identified using molecular techniques (alpha 1a/d, alpha 1b, and alpha 1c), whereas two subtypes of alpha 1ARs have been identified pharmacologically (alpha 1A and alpha 1B); however, controversies exist regarding how these two classification schemes relate to each other. In an attempt to clarify some of the controversies regarding classification of alpha 1AR subtypes, we have re-evaluated the distribution of mRNA for the cloned alpha 1AR subtypes (alpha 1a/d, alpha 1b, and alpha 1c) in various rat tissues thought to express alpha 1AR subtypes, as well as the human neuronal cell line SK-N-MC (a recently described model for pharmacologically defined alpha 1AAR and alpha 1BAR subtypes), using sensitive ribonuclease protection assay techniques. Total RNA extracted from various rat tissues and SK-N-MC cells was hybridized with rat and human alpha 1AR subtype-specific probes, respectively. In contrast to previously reported Northern blot analyses, alpha 1cAR mRNA is expressed in many rat tissues. Expression of alpha 1cAR mRNA is highest in those tissues that have been previously characterized by radioligand binding as expressing the classical, pharmacologically defined alpha 1AAR. Likewise, the human neuronal SK-N-MC cell line, classically thought to express pharmacological alpha 1AAR and alpha 1BAR subtypes, expresses both alpha 1a/dAR and alpha 1cAR mRNA and no alpha 1bAR mRNA. Collectively, these data suggest that the cloned alpha 1cAR subtype may represent the pharmacological alpha 1AAR, and they have important implications for merging pharmacological and molecular classifications of alpha 1AR subtypes.
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