Thealpha-1 (α₁)adrenergic receptor (or adrenoceptor) is aG protein-coupled receptor (GPCR) associated with theG_qheterotrimeric G protein. It consists of three highly homologous subtypes,α_1A-,α_1B-, andα_1D-adrenergic. 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 likenorepinephrine (noradrenaline) andepinephrine (adrenaline) signal through the α₁-adrenergic receptors in thecentral andperipheral 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 theα₂-adrenergic receptor, but also has specific effects of its own. α₁-receptors primarily mediatesmooth muscle contraction, but have important functions elsewhere as well.^[3] Theneurotransmitter norepinephrine has higher affinity for the α₁ receptor than does the hormoneadrenaline.

In smooth muscle cells ofblood vessels the principal effect of activation of these receptors isvasoconstriction. Blood vessels with α₁-adrenergic receptors are present in theskin, thesphincters^[4] ofgastrointestinal system,kidney (renal artery)^[5] andbrain.^[6] During thefight-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 internal urethral sphincter^[7] of theurinary bladder,^[8][9] although this effect is minor compared to the relaxing effect ofβ₂-adrenergic receptors. In other words, the overall effect of sympathetic stimuli on the bladder is relaxation, in order to inhibitmicturition upon anticipation of a stressful event. Other effects on smooth muscle are contraction in:

• Ureter
• Uterus (when pregnant): this is minor compared to the relaxing effects of the β₂ receptor, agonists of which—notably albuterol/salbutamol—were formerly^{[citation needed]} used to inhibit premature labor.
• Urethral sphincter
• Bronchioles (although minor to the relaxing effect of β₂ receptor on bronchioles)
• Iris dilator muscle^[4]
• Seminal tract,^[4] resulting inejaculation

Activation of α₁-adrenergic receptors producesanorexia and partially mediates the efficacy ofappetite suppressants likephenylpropanolamine andamphetamine in the treatment ofobesity.^[10] Norepinephrine has been shown to decreasecellular excitability in all layers of thetemporal cortex, including theprimary auditory cortex. In particular, norepinephrine decreasesglutamatergic excitatorypostsynaptic potentials by the activation of α₁-adrenergic receptors.^[11] Norepinephrine also stimulatesserotonin release by binding α₁-adrenergic receptors located on serotonergic neurons in the raphe.^[12]α₁-adrenergic receptor subtypes increase inhibition in the olfactory system, suggesting a synaptic mechanism for noradrenergic modulation of olfactory driven behaviors.^[13]

• Both positive and negativeinotropic effects onheart muscle^[8][14]
• Secretion fromsalivary gland^[8]
• Increase salivarypotassium levels
• Glycogenolysis andgluconeogenesis inliver.
• Secretion fromsweat glands^[8]
• Contraction of the urinary bladder urothelium and lamina propria^[15]
• Na⁺ reabsorption fromkidney^[8]
  • Stimulateproximal tubuleNHE3^[16]
  • Stimulateproximal tubule basolateralNa-K ATPase^[16]
• Activatemitogenic responses and regulate growth and proliferation of many cells
• Involved in the detection of mechanical feedback on thehypoglossal motor neurons which allow a long-term facilitation in respiration in response to repeatedapneas.^[17]

α₁-Adrenergic receptors are members of theG protein-coupled receptor superfamily. Upon activation, aheterotrimeric G protein,G_q, activatesphospholipase C (PLC), which causesphosphatidylinositol to be transformed intoinositol trisphosphate (IP₃) anddiacylglycerol (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]}

Variousheterocyclicantidepressants andantipsychotics are α₁-adrenergic receptor antagonists as well. This action is generally undesirable in such agents and mediatesside effects likeorthostatic hypotension, and headaches due to excessive vasodilation.

• Adrenergic receptor

• "Adrenoceptors".IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

• Adrenergic receptors
• Exercise biochemistry

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