Expression of α₁-adrenergic receptor subtype mRNA in rat tissues and human SK-N-MC neuronal cells: Implications for α₁-adrenergic receptor subtype classification

At least three subtypes of α₁-adrenergic receptors (α₁ARs) have been identified using molecular techniques (α(1a/d), α(1b), and α(1c)), whereas two subtypes of α₁ARs have been identified pharmacologically (α(1A) and α(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 α₁AR subtypes, we have re- evaluated the distribution of mRNA for the cloned α₁AR subtypes (α(1a/d), α(1b), and α(1c)) in various rat tissues thought to express α₁AR subtypes, as well as the human neuronal cell line SK-N-MC (a recently described model for pharmacologically defined α(1A)AR and α(1B)AR 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 α₁AR subtype-specific probes, respectively. In contrast to previously reported Northern blot analyses, α(1c)AR mRNA is expressed in many rat tissues. Expression of α(1c)AR mRNA is highest in those tissues that have been previously characterized by radioligand binding as expressing the classical, pharmacologically defined α(1A)AR. Likewise, the human neuronal SK-N-MC cell line, classically thought to express pharmacological α(1A)AR and α(1B)AR subtypes, expresses both α(1a/d)AR and α(1c)AR mRNA and no α(1b)AR mRNA. Collectively, these data suggest that the cloned α(1c)AR subtype may represent the pharmacological α(1A)AR, and they have important implications for merging pharmacological and molecular classifications of α₁AR subtypes.