Molecular Pharmacology of Alpha Adrenergic Receptors.

Catecholamines and adrenergic receptor antagonists have important effects, both in health and disease. At least 3 subtypes of alpha1 adrenergic receptors have been identified with a combination of pharmacological, radioligand binding and molecular cloning techniques. This heterogeneity leaves open the possibility that subtype specific drugs may be developed with enhanced specificity for alpha1 receptor subtypes in various cells. Alpha1 receptors in vascular and non-vascular smooth muscle are well known to promote smooth muscle contraction. In addition, these receptors play an important role in regulating smooth muscle cell growth although this is less fully appreciated. Specific subtypes of alpha1 receptors activate expression of a number of proto-oncogenes in smooth muscle cells. These effects of catecholamines are inhibited by release of nitric oxide from endothelial cells. In the setting of endothelial cell damage, the pharmacology of responsiveness of neointimal smooth muscle to catecholamines may differ from that of normal medial smooth muscle suggesting the possibility that novel adrenergic antagonists may have efficacy in modulating cell growth after injury.