EXPRESSION OF ALPHA(1)-ADRENERGIC RECEPTOR SUBTYPE MESSENGER-RNA IN RAT-TISSUES AND HUMAN SK-N-MC NEURONAL CELLS - IMPLICATIONS FOR ALPHA(1)-ADRENERGIC RECEPTOR SUBTYPE CLASSIFICATION

At least three subtypes of alpha(1)-adrenergic receptors (alpha(1)ARs) have been identified using molecular techniques (alpha(1a/d), alpha(1 b), and alpha(1c)), whereas two subtypes of alpha(1)ARs have been iden tified pharmacologically (alpha(1A) and alpha(1B)); however, controver sies exist regarding how these two classification schemes relate to ea ch other. In an attempt to clarify some of the controversies regarding classification of alpha(1)AR subtypes, we have re-evaluated the distr ibution of mRNA for the cloned alpha(1)AR subtypes (alpha(1a/d), alpha (1b), and alpha(1c)) in various rat tissues thought to express cr,AR s ubtypes, as well as the human neuronal cell line SK-N-MC (a recently d escribed model for pharmacologically defined alpha(1A)AR and alpha(1B) AR subtypes), using sensitive ribonuclease protection assay techniques . Total RNA extracted from various rat tissues and SK-N-MC cells was h ybridized with rat and human alpha(1)AR subtype-specific probes, respe ctively. In contrast to previously reported Northern blot analyses, al pha(1c)AR mRNA is expressed in many rat tissues. Expression of alpha(1 c)AR mRNA is highest in those tissues that have been previously charac terized by radioligand binding as expressing the classical, pharmacolo gically defined alpha(1A)AR. Likewise, the human neuronal SK-N-MC cell line, classically thought to express pharmacological alpha(1A)AR and alpha(1B)AR subtypes, expresses both alpha(1a/d)AR and alpha(1c)AR mRN A and no alpha(1b)AR mRNA. Collectively, these data suggest that the c loned alpha(1c)AR subtype may represent the pharmacological alpha(1A)A R, and they have important implications for merging pharmacological an d molecular classifications of alpha(1)AR subtypes.