I. Introduction a1-ADRENERGIC receptors are involved in a variety of important physiological processes, including control of blood pressure, appetite, and mood. These receptors belong to the class of cell-surface receptors which initiate signals in their target cells by increasing the concentration of free cytosolic Ca2 and thereby affecting the metabolic or contractile state ofthe cell. Recent advances in our understanding of membrane lipid biochemistry have led to the conclusion that these receptors control cytosolic Ca2 primarily by stimulating hydrolysis of a highly phosphorylated inositol phospholipid. The prod-a Work in the author’s laboratory during the preparation of this review was supported by NS 21325, DA 03413, and a grant from the Georgia Heart Association. uct of this hydrolysis, inositol 1, 4, 5-trisphosphate [Ins (1, 4, 5) P3], has been shown to release Ca2 sequestered in intracellular stores, particularly the endoplasmic reticulum.

Recent evidence suggests, however, that a1-adrenergic receptors do not have the same properties in all tissues. The existence of distinct subtypes of a1-adrenergic receptors has been supported by a variety of pharmacological approaches. Interestingly, it has also become clear from studies in smooth muscle that there are major differences in the importance of extracellular Ca2 in responses to a1-adrenergic receptor stimulation. In some tissues stored intracellular Ca2 is sufficient for normal responses, while other tissues require influx of Ca2 through specific membrane channels. Recent studies have raised the possibility that, in addition to the well-