alpha-1 adrenoceptor

• α1アドレナリン受容体、α1アドレノセプター

関

alpha-1 adrenergic receptor、alpha1 adrenergic receptor、alpha1 adrenoceptor

WordNet

1. first in order of importance; "the alpha male in the group of chimpanzees"; "the alpha star in a constellation is the brightest or main star"
2. the 1st letter of the Greek alphabet
3. the beginning of a series or sequence; "the Alpha and Omega, the first and the last, the beginning and the end"--Revelations
4. early testing stage of a software or hardware product; "alpha version"
5. any high mountain

PrepTutorEJDIC

1. アルファ(ギリシア語アルファベットの第1字A,α;英語のA,aに相当) / アルファ星(星座の主星)
2. 高山,高峰

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/04/05 16:09:36」(JST)

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[Wiki en表示]

See also: Adrenergic receptor

The alpha-1 (α₁) adrenergic receptor is a G protein-coupled receptor (GPCR) associated with the G_q heterotrimeric G-protein. It consists of three highly homologous subtypes, including α_1A-, α_1B-, and α_1D-adrenergic. Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α₁-adrenergic receptor in the central and peripheral nervous systems.

Effects

The α₁-adrenergic receptor has several general functions in common with the α₂-adrenergic receptor, but also has specific effects of its own.

General

Common (or still unspecified) effects include:

• Vasoconstriction of arteries to heart (coronary arteries)
• Vasoconstriction of veins
• Decrease motility of smooth muscle in gastrointestinal tract

Specific

The primary effect is on smooth muscle, which it mainly constricts.^{[citation needed]} This may result in bronchospasm and anaphylaxis if stimulated by oxymetazoline or other alpha 1 agonists.

Stimulators

• Norepinephrine
• Epinephrine
• Other substances:
  • Metaraminol
• Phenylephrine

Smooth muscle

In smooth muscle of blood vessels the principal effect is vasoconstriction. Blood vessels with α₁-adrenergic receptors are present in the skin, the sphincters of gastrointestinal system, kidney (renal artery) 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 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 are on smooth muscle are contraction in:

• Ureter
• Hairs (arrector pili muscles)
• Uterus (when pregnant)
• Urethral sphincter
• Bronchioles (although minor to the relaxing effect of β₂ receptor on bronchioles)
• Iris dilator muscle
• Seminal tract, resulting in ejaculation

In a few areas the result on smooth muscle is relaxation. These include:

• The rest of the GI tract, except for the sphincters
• Blood vessels of erectile tissue

Neuronal

Activation of α₁-adrenergic receptors produces anorexia and partially mediates the efficacy of appetite suppressants like phenylpropanolamine and amphetamine in the treatment of obesity. 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.

Other

• Positive inotropic effect on heart muscle (α₁<<β₁) (in other words, strengthening the force of contraction)
• Secretion from salivary gland
• Increase salivary potassium levels
• Glycogenolysis and gluconeogenesis from adipose tissue and liver.
• Secretion from sweat glands
• Na⁺ reabsorption from kidney
  • Stimulate proximal tubule NHE3
  • Stimulate proximal tubule basolateral Na-K ATPase
• 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.

Signaling cascade

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 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.

Activity during exercise

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]}

Ligands

Agonists

• Butcher's Broom (Ruscus aculeatus)
• Cirazoline
• Etilefrine
• Metaraminol
• Methoxamine
• Midodrine
• Naphazoline
• Oxymetazoline
• Phenylephrine (decongestant)
• Synephrine
• Tetrahydrozoline
• Xylometazoline

Antagonists

• Alfuzosin (used in benign prostatic hyperplasia
• Arotinolol
• Carvedilol (used in congestive heart failure; it is a non-selective beta blocker)
• Doxazosin (used in hypertension and benign prostatic hyperplasia)
• Indoramin
• Labetalol (used in hypertension; it is a mixed alpha/beta adrenergic antagonist)
• Moxisylyte
• Phenoxybenzamine
• Phentolamine (used in hypertensive emergencies; it is a nonselective alpha-antagonist)
• Prazosin (used in hypertension)
• Silodosin
• Tamsulosin (used in benign prostatic hyperplasia)
• Terazosin
• Tolazoline
• Trimazosin

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

See also

• Adrenergic receptor

References

External links

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

UpToDate Contents

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English Journal

• Stimulation of α1-adrenoceptors facilitates GABAergic transmission onto pyramidal neurons in the medial prefrontal cortex.

• Luo F1, Tang H2, Cheng ZY2.
• Neuroscience.Neuroscience.2015 Aug 6;300:63-74. doi: 10.1016/j.neuroscience.2015.04.070. Epub 2015 May 2.
• Whereas activation of α1-adrenoceptors (α1-ARs) modulates glutamatergic transmission, the roles of α1-ARs in GABAergic transmission in the medial prefrontal cortex (mPFC) are elusive. Here, we examined the effects of the α1-AR agonist phenylephrine (Phe) on GABAergic transmission onto pyramidal
• PMID 25943480

• Basal activity of voltage-gated Ca(2+) channels controls the IP3-mediated contraction by α1-adrenoceptor stimulation of mouse aorta segments.

• Leloup AJ1, Van Hove CE2, De Meyer GR3, Schrijvers DM4, Fransen P5.
• European journal of pharmacology.Eur J Pharmacol.2015 Aug 5;760:163-71. doi: 10.1016/j.ejphar.2015.04.011. Epub 2015 Apr 22.
• α1-Adrenoceptor stimulation of mouse aorta causes intracellular Ca(2+) release from sarcoplasmic reticulum Ca(2+) stores via stimulation of inositoltriphosphate (IP3) receptors. It is hypothesized that this Ca(2+) release from the contractile and IP3-sensitive Ca(2+) store is under the continuous d
• PMID 25913240

• Rayleigh light scattering detection of three α1-adrenoceptor antagonists coupled with high performance liquid chromatograph.

• Li AP1, Peng H1, Peng JD2, Zhou MQ1, Zhang J1.
• Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.Spectrochim Acta A Mol Biomol Spectrosc.2015 Aug 5;147:178-84. doi: 10.1016/j.saa.2015.02.062. Epub 2015 Mar 11.
• Herein, a Rayleigh light-scattering (RLS) detection method combined with high performance liquid chromatograph (HPLC) without any post-column probe was developed for the separation and determination of three α1-adrenoceptor antagonists. The quantitative analysis is benefiting from RLS signal enhanc
• PMID 25840026

Japanese Journal

• Tamsulosin Potently and Selectively Antagonizes Human Recombinant α₁A/₁D-Adrenoceptors : Slow Dissociation from the α₁A-Adrenoceptor May Account for Selectivity for α₁A-Adrenoceptor over α₁B-Adrenoceptor Subtype

• Sato Shuichi,Hatanaka Toshiki,Yuyama Hironori [他],Ukai Masashi,Noguchi Yukiko,Ohtake Akiyoshi,Taguchi Katsunari,Sasamata Masao,Miyata Keiji
• Biological and Pharmaceutical Bulletin 35(1), 72-77, 2012
• … We determined the binding affinity of tamsulosin, a selective α1-adrenoceptor antagonist, for human α1-adrenoceptor subtypes in comparison with those of other α1-adrenoceptor antagonists including silodosin, prazosin, 5-methylurapidil, terazosin, alfuzosin, nafopidil, urapidil and BMY7378. …
• NAID 130001872345

• Effects of three types of alpha-1 adrenoceptor blocker on lower urinary tract symptoms and sexual function in males with benign prostatic hyperplasia

• YOKOYAMA Teruhiko,HARA Ryoei,FUKUMOTO Kazuhiko,FUJII Tomohiro,JO Yoshimasa,MIYAJI Yoshiyuki,NAGAI Atsushi,SONE Atsushi
• International journal of urology 18(3), 225-230, 2011-03-01
• NAID 10030822191

• Safety and Pharmacokinetic Studies of Silodosin, a New .ALPHA.1A-Adrenoceptor Selective Antagonist, in Healthy Chinese Male Subjects

• Zhou Ying,Sun Pei-Hong,Liu Yu-Wang [他],Zhao Xia,Meng Lei,Cui Yi-Min
• Biological and Pharmaceutical Bulletin 34(8), 1240-1245, 2011
• … To assess the safety and pharmacokinetics via multiple-dosing, 12 subjects were included as a group (4 mg once daily at day 1 and day 7; … The accumulation ratio of the AUC value was 1.55 by comparing the multiple-dosing with the single-dosing. …
• NAID 130000936593

Related Links

• Alpha-1 adrenergic receptor - Wikipedia, the free encyclopedia

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 ...

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★リンクテーブル★

リンク元	「alpha-1 adrenergic receptor」
関連記事	「adrenoceptor」「alpha」

「alpha-1 adrenergic receptor」

　　[★]

• α1アドレナリン受容体、α1アドレナリンレセプター

関

adrenergic alpha-1 receptor、alpha-1 adrenoceptor、alpha1 adrenergic receptor、alpha1 adrenoceptor

「adrenoceptor」

　　[★]

• アドレナリン受容体、アドレノセプター

関

adrenergic receptor、adrenoreceptor

「alpha」

　　[★]

α、アルファ

関

alfa