Alpha-1 adrenergic receptor 5023296 219488853 2008-06-15T13:50:29Z Alaibot 1324179 Robot: sorting stub (based on existing categorisation) The '''alpha-1 adrenergic receptor''' (α<sub>1</sub>-AR) is an [[adrenergic receptor]] with the primary effect of [[vasoconstriction]]. ==Effect== The α<sub>1</sub> receptor has several, general, functions in common with other α-receptors, but also has specific effects. ===General=== Common (or still unspecified) effects include: * [[Vasoconstriction]] of [[arteries]] to [[heart]] ([[coronary arteries]]).<ref name="pmid2887122">{{cite journal | author = Woodman OL, Vatner SF | title = Coronary vasoconstriction mediated by α<sub>1</sub>- and α<sub>2</sub>-adrenoceptors in conscious dogs | journal = Am. J. Physiol. | volume = 253 | issue = 2 Pt 2 | pages = H388–93 | year = 1987 | pmid = 2887122 | doi = | issn = | url = http://ajpheart.physiology.org/cgi/content/abstract/253/2/H388 }}</ref> * Vasoconstriction of [[veins]]<ref name="pmid9280371">{{cite journal | author = Elliott J | title = Alpha-adrenoceptors in equine digital veins: evidence for the presence of both α<sub>1</sub> and α<sub>2</sub>-receptors mediating vasoconstriction | journal = J. Vet. Pharmacol. Ther. | volume = 20 | issue = 4 | pages = 308–17 | year = 1997 | pmid = 9280371 | doi = 10.1046/j.1365-2885.1997.00078.x | issn = }}</ref> * Decrease motility of [[smooth muscle]] in [[gastrointestinal tract]]<ref name="pmid2889649">{{cite journal | author = Sagrada A, Fargeas MJ, Bueno L | title = Involvement of α<sub>1</sub> and α<sub>2</sub> adrenoceptors in the postlaparotomy intestinal motor disturbances in the rat | journal = Gut | volume = 28 | issue = 8 | pages = 955–9 | year = 1987 | pmid = 2889649 | doi = 10.1136/gut.28.8.955 | issn = }}</ref> ===Specific=== The primary effect is on [[smooth muscle]], which mainly constrict. However, there are other functions as well. ====Smooth muscle==== In smooth muscle of [[blood vessel]]s the principal effect is [[vasoconstriction]]. Blood vessels with α<sub>1</sub> receptors are present in the [[skin]], the [[sphincters]]<ref name=Rang163/> of [[gastrointestinal system]], [[kidney]] ([[renal artery]])<ref name="pmid6270306">{{cite journal | author = Schmitz JM, Graham RM, Sagalowsky A, Pettinger WA | title = Renal α<sub>1</sub> and α<sub>2</sub> adrenergic receptors: biochemical and pharmacological correlations | journal = J. Pharmacol. Exp. Ther. | volume = 219 | issue = 2 | pages = 400–6 | year = 1981 | pmid = 6270306 | doi = | issn = | url = http://jpet.aspetjournals.org/cgi/content/abstract/219/2/400 }}</ref> and [[brain]].<ref>[http://cim.ucdavis.edu/masters/sessions2002/session4_ica.doc Circulation & Lung Physiology I] M.A.S.T.E.R. Learning Program, UC Davis School of Medicine</ref> During the [[fight-or-flight response]] vasoconstriction results in the decreased blood flow to these organs. This accounts for an individual's skin appearing pale when frightened. It also induces contraction of the [[urinary bladder]]<ref name="purves">{{cite book | author = Fitzpatrick, David; Purves, Dale; Augustine, George | title = Neuroscience | publisher = Sinauer | location = Sunderland, Mass | year = 2004 | | edition = Third Edition | chapter = Table 20:2 | pages = | isbn = 0-87893-725-0 | oclc = | doi = }}</ref><ref name="pmid14634460">{{cite journal | author = Chou EC, Capello SA, Levin RM, Longhurst PA | title = Excitatory α<sub>1</sub>-adrenergic receptors predominate over inhibitory β-receptors in rabbit dorsal detrusor | journal = J. Urol. | volume = 170 | issue = 6 Pt 1 | pages = 2503–7 | year = 2003 | pmid = 14634460 | doi = 10.1097/01.ju.0000094184.97133.69 | issn = }}</ref>, although this effect is minor compared to the relaxing effect of [[β-2 adrenergic receptor]]s. 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]] *[[hair]]s ([[arrector pili muscles]]) *[[uterus]] (when pregnant) *[[urethral sphincter]] *[[bronchioles]] (although minor to the relaxing effect of β<sub>2</sub> receptor on bronchioles) *[[iris dilator muscle]]<ref name=Rang163> {{cite book |author=Rang, H. P. |title=Pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2003 |pages= |isbn=0-443-07145-4 |oclc= |doi=}} Page 163 </ref> *[[seminal tract]]<ref name=Rang163/>, resulting in [[ejaculation]] In a few areas the result on smooth muscle is relaxation. These include: *The rest of the [[Gastrointestinal tract|GI tract]] than the sphincters.<ref name=Rang163/> *Blood vessels of [[erectile tissue]].<ref name="pmid17115072">{{cite journal | author = Morton JS, Daly CJ, Jackson VM, McGrath JC | title = Alpha<sub>1A</sub>-adrenoceptors mediate contractions to phenylephrine in rabbit penile arteries | journal = Br. J. Pharmacol. | volume = 150 | issue = 1 | pages = 112–20 | year = 2007 | pmid = 17115072 | doi = 10.1038/sj.bjp.0706956 | issn = }}</ref> ====Other==== *Positive [[ionotropic effect]] on [[heart muscle]].<ref name=purves/> (α<sub>1</sub><<β<sub>1</sub>).<ref name=purves/> *&uarr;Secretion from [[salivary gland]].<ref name=purves/> *Increase salivary [[potassium]] levels. *[[Glycogenolysis]] and [[gluconeogenesis]] from [[adipose tissue]]<ref name=purves/> and [[liver]]. *Secretion from [[sweat gland]]s.<ref name=purves/> *[[sodium|Na<sup>+</sup>]] reabsorption from [[kidney]].<ref name=purves/> **Stimulate [[proximal tubule]] [[NHE3]]<ref name=boron787> {{cite book |author=Walter F., PhD. Boron |title=Medical Physiology: A Cellular And Molecular Approaoch |publisher=Elsevier/Saunders |location= |year= |pages= |isbn=1-4160-2328-3 |oclc= |doi=}} Page 787 </ref> **Stimulate [[proximal tubule]] basolateral [[Na-K ATPase]]<ref name=boron787/> *Activate [[mitogenic]] responses and regulate growth and proliferation of many cells. ==Activity During Exercise== During exercise these alpha-1 receptors can be selectively blocked by sympathetic nervous activity, allowing the beta-2 receptors (which mediate vasodilation) to dominate. Note that only the alpha-1 receptors in exercising muscle will be blocked. Resting muscle will not have its alpha-1 receptors blocked, and hence the overall effect there will be alpha-1 mediated vasocontriction. ==Mechanism== Alpha<sub>1</sub>-adrenergic receptors are members of the [[G protein-coupled receptor]] superfamily. Upon activation, a [[heterotrimeric G protein]], [[Gq alpha subunit|G<sub>q</sub>]], activates [[phospholipase C]] (PLC), which causes an increase in [[inositol trisphosphate|IP<sub>3</sub>]] and [[calcium]]. This triggers all other effects. ==Agonists== Agonists include: * [[noradrenaline]] * [[adrenaline]] * [[isoprenaline]] * [[phenylephrine]]*<ref name=Rang163/> ([[decongestant]]) * [[methoxamine]]*<ref name=Rang163/> * [[cirazoline]]* <nowiki>*</nowiki> denotes [[selective agonist]]s to the receptor. Noradrenaline has higher [[receptor affinity]] than has adrenaline, which, in turn has much higher affinity than isoprenaline.<ref name=Rang163/> ==Antagonists== Antagonists are various ''[[alpha blocker]]s: *[[mirtazapine]] ([[noradrenergic and specific serotonergic antidepressant|NaSSA]]) *[[phenoxybenzamine]] (in [[hypertension]]) *[[phentolamine]] (in [[hypertensive emergencies]]) *[[prazosin]]*<ref name=Rang163/> (in [[hypertension]]) *[[tamsulosin]] (in [[benign prostatic hyperplasia|BPH]]) *[[terazosin]] (in [[benign prostatic hyperplasia|BPH]] and hypertension) *[[doxazocin]]*<ref name=Rang163/> (in [[benign prostatic hyperplasia|BPH]] and hypertension) <nowiki>*</nowiki> denotes [[selective antagonist]]s to the receptor. ==Subtypes== There are 3 α<sub>1</sub>-AR subtypes: [[alpha-1A]], [[alpha-1B|-1B]] and [[alpha-1D|-1D]], all of which signal through the G<sub>q/11</sub> family of G-proteins and different subtypes show different patterns of activation. ==See also== *Other [[adrenergic receptors]] **[[Alpha-2 adrenergic receptor]] **[[Beta-1 adrenergic receptor]] **[[Beta-2 adrenergic receptor]] **[[Beta-3 adrenergic receptor]] ==References== {{Reflist|2}} {{transmembranereceptor-stub}} {{G protein-coupled receptors}} [[Category:Adrenergic receptors‎]] [[Category:G protein coupled receptors]] [[de:Α1-Adrenozeptor]] [[es:Receptor adrenérgico alfa 2]]