The endogenous catecholamines epinephrine and norepinephrine have profound effects on smooth muscle activity, cardiac function, carbohydrate and fat metabolism, hormone secretion, neurotransmitter release, and central nervous system actions. These activities are mediated by GPCRs belonging to two subfamilies, the alpha- and beta-adrenoceptors. The three members of the alpha1 subclass of adrenoceptors, alpha1A, alpha1B and alpha1D, couple to Gq, and promote contraction of vascular and urinary tract smooth muscle, relaxation of intestinal smooth muscle, increased contractile force in the heart, and glycogenolysis and gluconeogenesis in the liver. The different subtypes have overlapping distributions and variably contribute to these effects depending on species and tissue. The alpha1D adrenergic receptor mediates smooth muscle contraction in several tissues. In the vasculature, activation of alpha1D increases blood pressure. In the urinary tract, alpha1D promotes bladder contraction. Antagonists of alpha1 receptors are used to treat bladder outlet obstruction, and this effect is thought to be mediated by alpha1D. The alpha1D adrenergic receptors has a relatively long N-terminal extracellular domain, and truncation of this domain has been shown to increase expression of the receptor at the cell surface.