Alpha-1 adrenergic receptor

alpha-1 (α₁) adrenergic receptors are G protein-coupled receptors (GPCRs) associated with the G_q heterotrimeric G protein. α₁-adrenergic receptors are subdivided into three highly homologous subtypes, i.e., α_1A-, α_1B-, and α_1D-adrenergic receptor subtypes. There is no α_1C receptor. At one time, there was a subtype known as α_1C, but it was found to be identical to the previously discovered α_1A receptor subtype.^[1] To avoid confusion, naming was continued with the letter D. Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α₁-adrenergic receptors in the central and peripheral nervous systems. The crystal structure of the α_1B-adrenergic receptor subtype has been determined in complex with the inverse agonist (+)-cyclazosin.^[2]

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.^[3] The neurotransmitter norepinephrine has higher affinity for the α₁ receptor than does the hormone adrenaline.

α₁-Adrenergic receptors are members of the G protein-coupled receptor superfamily. Upon activation, a heterotrimeric G protein, G_q, activates phospholipase C (PLC), which causes phosphatidylinositol to be transformed into inositol trisphosphate (IP₃) and diacylglycerol (DAG). 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.

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.^[18] 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.^[18]

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.^{[citation needed]}

Various heterocyclic antidepressants and antipsychotics are α₁-adrenergic receptor antagonists as well. This action is generally undesirable in such agents and mediates side effects like orthostatic hypotension, and headaches due to excessive vasodilation.

• Adrenergic receptor