The alpha-1adrenergic receptor is a G protein-coupled receptor associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic. Catecholamines like norepinephrine and epinephrine signal through the α1-adrenergic receptor in the central and peripheral nervous systems. There is no α1C receptor. At one time, there was a subtype known as α1C, but it was found to be identical to the previously discovered α1A receptor subtype. To avoid confusion, naming was continued with the letter D.
Effects
The α1-adrenergic receptor has several general functions in common with the α2-adrenergic receptor, but also has specific effects of its own. α1-receptors primarily mediate smooth muscle contraction, but have important functions elsewhere as well. The neurotransmitter norepinephrine has higher affinity for the α1 receptor than does the hormone epinephrine/adrenaline.
Smooth muscle
In smooth muscle cells of blood vessels the principal effect of activation of these receptors is vasoconstriction. Blood vessels with α1-adrenergic receptors are present in the skin, the sphincters of gastrointestinal system, kidney and brain. During the fight-or-flight response vasoconstriction results in decreased blood flow to these organs. This accounts for the pale appearance of the skin of an individual when frightened. It also induces contraction of the urinary bladder, although this effect is minor compared to the relaxing effect of β2-adrenergic receptors. In other words, the overall effect of sympathetic stimuli on the bladder is relaxation, in order to inhibit micturition upon anticipation of a stressful event. Other effects on smooth muscle are contraction in:
Uterus : this is minor compared to the relaxing effects of the β2 receptor, agonists of which - notably albuterol/salbutamol - were formerly used to inhibit premature labor.
Activate mitogenic responses and regulate growth and proliferation of many cells
Involved in the detection of mechanical feedback on the hypoglossalmotor neurons which allow a long-term facilitation in respiration in response to repeated apneas.
Signaling cascade
α1-Adrenergic receptors are members of the G protein-coupled receptor superfamily. Upon activation, a heterotrimeric G protein, Gq, activates phospholipase C, which causes phosphatidylinositol to be transformed into inositol triphosphate and diacylglycerol. While DAG stays near the membrane, IP3 diffuses into the cytosol and to find the IP3 receptor on the endoplasmic reticulum, triggering calcium release from the stores. This triggers further effects, primarily through the activation of an enzyme Protein Kinase C. This enzyme, as a kinase, functions by phosphorylation of other enzymes causing their activation, or by phosphorylation of certain channels leading to the increase or decrease of electrolyte transfer in or out of the cell.
Activity during exercise
During exercise, α1-adrenergic receptors in active muscles are attenuated in an exercise intensity-dependent manner, allowing the β2-adrenergic receptors which mediate vasodilation to dominate. In contrast to α2-adrenergic receptors, α1-adrenergic-receptors in the arterial vasculature of skeletal muscle are more resistant to inhibition, and attenuation of α1-adrenergic-receptor-mediated vasoconstriction only occurs during heavy exercise. Note that only active muscle α1-adrenergic receptors will be blocked. Resting muscle will not have its α1-adrenergic receptors blocked, and hence the overall effect will be α1-adrenergic-mediated vasoconstriction.
