Alpha 1-adrenergic receptor subtypes.

Investigators have not yet reached a consensus on the number and signaling mechanisms of alpha 1-adrenergic receptor (AR) subtypes. Two native subtypes (alpha 1A and alpha 1B) can be distinguished pharmacologically, and three subtypes (alpha 1B, alpha 1C, and alpha 1D) have been cloned. One of the cloned subtypes (alpha 1D) was originally thought to encode the pharmacologically defined alpha 1A subtype. However, recent data suggest otherwise, and many investigators now agree that the alpha 1A subtype has probably not yet been cloned. The relationship between the cloned receptors and the native subtypes must be understood, and any additional cDNA clones obtained, before the drug specificities and second messenger pathways of alpha 1-AR subtypes can be clearly defined. Little is yet known about the cellular and tissue distribution of these subtypes, their developmental profiles, or their functional importance. Molecular cloning of complementary DNA sequences for the remaining subtypes will help to clarify the number and properties of these subtypes. Identification of drugs that can selectively target particular subtypes is an important goal that may result in therapeutic advances in numerous disease states, including benign prostatic hyperplasia. The newly recognized complexity of the adrenergic receptors presents us with both important challenges and new therapeutic targets. The potential impact of this field on medical therapeutics remains to be clearly defined.