Alpha-1 adrenergic receptor
The alpha-1 (α1) adrenergic receptor is a G protein-coupled receptor (GPCR) associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic. Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α1-adrenergic receptor in the central and peripheral nervous systems.
The α1-adrenergic receptor has several general functions in common with the α2-adrenergic receptor, but also has specific effects of its own.
Common (or still unspecified) effects include:
- Vasoconstriction of arteries to heart (coronary arteries)1
- Vasoconstriction of veins2
- Decrease motility of smooth muscle in gastrointestinal tract3
- Other substances:
In smooth muscle of blood vessels the principal effect is vasoconstriction. Blood vessels with α1-adrenergic receptors are present in the skin, the sphincters4 of gastrointestinal system, kidney (renal artery)5 and brain.6 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,78 although this effect is minor compared to the relaxing effect of β3-adrenergic receptors. In other words, the overall effect of sympathetic stimuli on the bladder is relaxation, in order to delay micturition during stress. Other effects on smooth muscle are contraction in:
- Hairs (arrector pili muscles)
- Uterus (when pregnant)
- Urethral sphincter
- Bronchioles (although minor to the relaxing effect of β2 receptor on bronchioles)
- Iris dilator muscle4
- Seminal tract,4 resulting in ejaculation
In a few areas the result on smooth muscle is relaxation. These include:
Activation of α1-adrenergic receptors produces anorexia and partially mediates the efficacy of appetite suppressants like phenylpropanolamine and amphetamine in the treatment of obesity.10 Norepinephrine has been shown to decrease cellular excitability in all layers of the temporal cortex, including the primary auditory cortex. In particular, norepinephrine decreases glutamatergic excitatory postsynaptic potentials by the activation of α1-adrenergic receptors.11
- Positive inotropic effect on heart muscle7 (α1<<β1)7 (in other words, strengthening the force of contraction)
- Secretion from salivary gland7
- Increase salivary potassium levels
- Glycogenolysis and gluconeogenesis from adipose tissue7 and liver.
- Secretion from sweat glands7
- Na+ reabsorption from kidney7
- Activate mitogenic responses and regulate growth and proliferation of many cells
- Involved in the detection of mechanical feedback on the hypoglossal motor neurons which allow a long-term facilitation in respiration in response to repeated apneas.13
α1-Adrenergic receptors are members of the G protein-coupled receptor superfamily. Upon activation, a heterotrimeric G protein, Gq, activates phospholipase C (PLC), which causes an increase in IP3 and calcium. 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 these α1-adrenergic receptors can be selectively blocked by sympathetic nervous activity, allowing the β2-adrenergic receptors (which mediate vasodilation) to dominate. Note that only the α1-adrenergic receptors in active muscle 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 extrapyramidal symptoms
- Woodman OL, Vatner SF (1987). "Coronary vasoconstriction mediated by α1- and α2-adrenoceptors in conscious dogs". Am. J. Physiol. 253 (2 Pt 2): H388–93. PMID 2887122.
- Elliott J (1997). "Alpha-adrenoceptors in equine digital veins: evidence for the presence of both α1 and α2-receptors mediating vasoconstriction". J. Vet. Pharmacol. Ther. 20 (4): 308–17. doi:10.1046/j.1365-2885.1997.00078.x. PMID 9280371.
- Sagrada A, Fargeas MJ, Bueno L (1987). "Involvement of alpha-1 and alpha-2 adrenoceptors in the postlaparotomy intestinal motor disturbances in the rat". Gut 28 (8): 955–9. doi:10.1136/gut.28.8.955. PMC 1433140. PMID 2889649.
- Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 163
- Schmitz JM, Graham RM, Sagalowsky A, Pettinger WA (1981). "Renal α1 and α2 adrenergic receptors: biochemical and pharmacological correlations". J. Pharmacol. Exp. Ther. 219 (2): 400–6. PMID 6270306.
- Circulation & Lung Physiology I M.A.S.T.E.R. Learning Program, UC Davis School of Medicine
- Fitzpatrick, David; Purves, Dale; Augustine, George (2004). "Table 20:2". Neuroscience (Third ed.). Sunderland, Mass: Sinauer. ISBN 0-87893-725-0.
- Chou EC, Capello SA, Levin RM, Longhurst PA (2003). "Excitatory α1-adrenergic receptors predominate over inhibitory β-receptors in rabbit dorsal detrusor". J. Urol. 170 (6 Pt 1): 2503–7. doi:10.1097/01.ju.0000094184.97133.69. PMID 14634460.
- Morton JS, Daly CJ, Jackson VM, McGrath JC (2007). "α1A-Adrenoceptors mediate contractions to phenylephrine in rabbit penile arteries". Br. J. Pharmacol. 150 (1): 112–20. doi:10.1038/sj.bjp.0706956. PMC 2013850. PMID 17115072.
- Cheng JT, Kuo DY (2003). "Both alpha1-adrenergic and D(1)-dopaminergic neurotransmissions are involved in phenylpropanolamine-mediated feeding suppression in mice". Neuroscience Letters 347 (2): 136–8. doi:10.1016/S0304-3940(03)00637-2. PMID 12873745.
- Dinh, L; Nguyen T, Salgado H, Atzori M (2009). "Norepinephrine homogeneously inhibits alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate- (AMPAR-) mediated currents in all layers of the temporal cortex of the rat". Neurochem Res 34 (11): 1896–906. doi:10.1007/s11064-009-9966-z. PMID 19357950.
- Walter F., PhD. Boron (2005). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. ISBN 1-4160-2328-3. Page 787
- Tadjalli, Arash; Duffin, James; Peever, John (2010). "Identification of a novel form of noradrenergic-dependent respiratory motor plasticity triggered by vagal feedback". The Journal of Neuroscience 30 (50): 16886–16895. doi:10.1523/JNEUROSCI.3394-10.2010. PMID 21159960.
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- "Adrenoceptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.