Adrenergic receptor: Difference between revisions
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==Modulation of receptor sensitivity and expression== | ==Modulation of receptor sensitivity and expression== | ||
Adrenergic receptor sensitivity is reduced by the agonist terbutaline.<ref name="pmid8564101">{{cite journal| author=Hjemdahl P, Zetterlund A, Larsson K| title=Beta 2-agonist treatment reduces beta 2-sensitivity in alveolar macrophages despite corticosteroid treatment. | journal=Am J Respir Crit Care Med | year= 1996 | volume= 153 | issue= 2 | pages= 576-81 | pmid=8564101 | doi= | pmc= | url= }} </ref> [[Corticosteroid]]s increase the expression of beta2-receptors.<ref name="pmid12464934">{{cite journal| author=Adcock IM, Maneechotesuwan K, Usmani O| title=Molecular interactions between glucocorticoids and long-acting beta2-agonists. | journal=J Allergy Clin Immunol | year= 2002 | volume= 110 | issue= 6 Suppl | pages= S261-8 | pmid=12464934 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12464934 }} </ref><ref name="pmid11843317">{{cite journal| author=Barnes PJ| title=Scientific rationale for inhaled combination therapy with long-acting beta2-agonists and corticosteroids. | journal=Eur Respir J | year= 2002 | volume= 19 | issue= 1 | pages= 182-91 | pmid=11843317 | doi= | pmc= | url= }} </ref> | Adrenergic receptor sensitivity is reduced by the [[adrenergic beta-agonist]] terbutaline.<ref name="pmid8564101">{{cite journal| author=Hjemdahl P, Zetterlund A, Larsson K| title=Beta 2-agonist treatment reduces beta 2-sensitivity in alveolar macrophages despite corticosteroid treatment. | journal=Am J Respir Crit Care Med | year= 1996 | volume= 153 | issue= 2 | pages= 576-81 | pmid=8564101 | doi= | pmc= | url= }} </ref> [[Corticosteroid]]s increase the expression of beta2-receptors.<ref name="pmid12464934">{{cite journal| author=Adcock IM, Maneechotesuwan K, Usmani O| title=Molecular interactions between glucocorticoids and long-acting beta2-agonists. | journal=J Allergy Clin Immunol | year= 2002 | volume= 110 | issue= 6 Suppl | pages= S261-8 | pmid=12464934 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12464934 }} </ref><ref name="pmid11843317">{{cite journal| author=Barnes PJ| title=Scientific rationale for inhaled combination therapy with long-acting beta2-agonists and corticosteroids. | journal=Eur Respir J | year= 2002 | volume= 19 | issue= 1 | pages= 182-91 | pmid=11843317 | doi= | pmc= | url= }} </ref> | ||
Adrenergic receptor may be up-regulated with increased density of receptors [[adrenergic beta-antagonist]]s which may contribute to withdrawal syndromes.<ref name="pmid6093157">{{cite journal| author=Piantanelli L, Giunta S, Basso A, Cognini G, Andreoni A, Paciaroni E| title=Atenolol-induced regulation of leukocyte beta 2-adrenoceptors in hypertension. | journal=Pharmacology | year= 1984 | volume= 29 | issue= 4 | pages= 210-4 | pmid=6093157 | doi= | pmc= | url= }} </ref> | |||
==References== | ==References== | ||
Revision as of 21:51, 12 January 2011
In biochemistry, adrenergic receptors are cell surface receptors of the G-protein-coupled receptor type that are in the sympathetic nervous system and are "cell-surface proteins that bind epinephrine and/or norepinephrine with high affinity and trigger intracellular changes. The two major classes of adrenergic receptors, alpha and beta, were originally discriminated based on their cellular actions but now are distinguished by their relative affinity for characteristic synthetic ligands. Adrenergic receptors may also be classified according to the subtypes of G-proteins with which they bind; this scheme does not respect the alpha-beta distinction."[1]
After binding, signal transduction activates the second messenger systems adenyl cyclase-cyclic AMP primarily and also cyclic GMP which then activates protein kinases.
Classification
alpha-Adrenergic Receptors
Phenoxybenzamine is a non-selective antagonist of both alpha-1 receptors and alpha-2 receptors.
alpha-1 receptors
Alpha-1 adrenergic receptors are a "subclass of alpha-adrenergic receptors (Receptors, Adrenergic, alpha). Alpha-1 Adrenergic receptors can be pharmacologically discriminated, e.g., by their high affinity for the agonist phenylephrine and the antagonist prazosin. They are widespread, with clinically important concentrations in the liver, the heart, vascular, intestinal, and genitourinary smooth muscle, and the central and peripheral nervous systems."[2] Their functions include vasoconstriction.
Agonists are sympathomimetic and are vasoconstrictor agents. Examples include:
- Nasal decongestants such as phenylephrine which treat nasal congestion by causing vasoconstriction.
- Midodrine is an agonist that is used for orthostatic hypotension and hepatorenal syndrome.
Antagonists, such as prazosin, are used to treat hypertension by blocking vasoconstriction.
alpha-2 receptors
Alpha-2 adrenergic receptors are a "subclass of alpha-adrenergic receptors (Receptors, adrenergic, alpha). Alpha-2 Adrenergic receptors can be pharmacologically discriminated, e.g., by their high affinity for the agonist clonidine and the antagonist yohimbine. They are found on pancreatic beta cells, platelets, and vascular smooth muscle, as well as both pre- and postsynaptically in the central and peripheral nervous systems."[3]
Agonists, such as clonidine, are used to treat hypertension.
Antagonists, such as yohimbine, are used to treat erectile dysfunction.
beta-Adrenergic Receptors
beta-1 receptors
Beta-1 adrenergic receptors are a "subclass of beta-adrenergic receptors (receptors, adrenergic, beta). Beta-1 adrenergic receptors are equally sensitive to epinephrine and norepinephrine and bind the agonist dobutamine and the antagonist metoprolol with high affinity. They are found in the heart, juxtaglomerular cells, and in the central and peripheral nervous systems."[4]
Adrenergic beta-agonists include cardiotonic agents such as dobutamine and dopamine which are used to treat circulatory shock by increasing heart contractility.
Adrenergic beta-antagonists that are selective for the beta-1 receptor such as metoprolol and atenolol, are used to treat hypertension and tachyarrythmias.
beta-2 receptors
Beta-2 adrenergic receptors are a "subclass of beta-adrenergic receptors (receptors, adrenergic, beta). Beta-2 Adrenergic receptors are more sensitive to epinephrine than to norepinephrine and have a high affinity for the agonist terbutaline. They are widespread, with clinically important roles in skeletal muscle, liver, and vascular, bronchial, gastrointestinal, and genitourinary smooth muscle."[5] Their functions include vasodilation.
Adrenergic beta-agonists, such as terbutaline, are used to treat asthma by preventing bronchoconstriction.
beta-3 receptors
Beta-3 adrenergic receptors are a "subclass of beta-adrenergic receptors (receptors, adrenergic, beta). Beta-3 adrenergic receptors are the predominant beta-adrenergic receptor type expressed in white and brown adipocytes and are involved in modulating energy metabolism and thermogenesis."[6]
Genetic polymorphisms
Genetic polymorphisms of the beta-1 receptor may affect responses to adrenergic beta-antagonists in the treatment of heart failure[7] and in preventing cardiac complications during perioperative care.[8]
Single-nucleotide polymorphism of the beta-1 (ADRB1) adrenergic receptor, specifically c.389A>G, may increase cardiac ischemia and SNP of the beta-2 (ADRB2) adrenergic receptor, specifically, c.16G>A SNP of the 4 SNPs studied, may increase hypotension in perioperative care.[8]
Single-nucleotide polymorphism of the beta-2 (ADRB2) adrenergic receptor, specifically c.46G>A and c.79C>G of the four SNPs studied, may affect the response to adrenergic beta-antagonist treatment of acute coronary syndrome.[9]
Genetic polymorphisms of alpha-2C (ADRA2C) may affect the response to adrenergic beta-antagonist treatment of heart failure.[10]
Modulation of receptor sensitivity and expression
Adrenergic receptor sensitivity is reduced by the adrenergic beta-agonist terbutaline.[11] Corticosteroids increase the expression of beta2-receptors.[12][13]
Adrenergic receptor may be up-regulated with increased density of receptors adrenergic beta-antagonists which may contribute to withdrawal syndromes.[14]
References
- ↑ Anonymous. Receptors, Adrenergic. National Library of Medicine. Retrieved on 2008-01-21.
- ↑ Anonymous. Receptors, Adrenergic, alpha-1. National Library of Medicine. Retrieved on 2008-01-16.
- ↑ Anonymous. Receptors, Adrenergic, alpha-2. National Library of Medicine. Retrieved on 2008-01-16.
- ↑ Anonymous. Receptors, Adrenergic, beta-1. National Library of Medicine. Retrieved on 2008-01-16.
- ↑ Anonymous. Receptors, Adrenergic, beta-2. National Library of Medicine. Retrieved on 2008-01-16.
- ↑ Anonymous. Receptors, Adrenergic, beta-3. National Library of Medicine. Retrieved on 2008-01-16.
- ↑ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 109630. World Wide Web URL: http://omim.org/.
- ↑ 8.0 8.1 Zaugg M, Bestmann L, Wacker J, et al. (July 2007). "Adrenergic receptor genotype but not perioperative bisoprolol therapy may determine cardiovascular outcome in at-risk patients undergoing surgery with spinal block: the Swiss Beta Blocker in Spinal Anesthesia (BBSA) study: a double-blinded, placebo-controlled, multicenter trial with 1-year follow-up". Anesthesiology 107 (1): 33–44. DOI:10.1097/01.anes.0000267530.62344.a4. PMID 17585213. Research Blogging.
Cite error: Invalid
<ref>tag; name "pmid17585213" defined multiple times with different content - ↑ Lanfear DE, Jones PG, Marsh S, Cresci S, McLeod HL, Spertus JA (2005). "Beta2-adrenergic receptor genotype and survival among patients receiving beta-blocker therapy after an acute coronary syndrome.". JAMA 294 (12): 1526-33. DOI:10.1001/jama.294.12.1526. PMID 16189366. Research Blogging.
- ↑ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 104250. World Wide Web URL: http://omim.org/.
- ↑ Hjemdahl P, Zetterlund A, Larsson K (1996). "Beta 2-agonist treatment reduces beta 2-sensitivity in alveolar macrophages despite corticosteroid treatment.". Am J Respir Crit Care Med 153 (2): 576-81. PMID 8564101. [e]
- ↑ Adcock IM, Maneechotesuwan K, Usmani O (2002). "Molecular interactions between glucocorticoids and long-acting beta2-agonists.". J Allergy Clin Immunol 110 (6 Suppl): S261-8. PMID 12464934. [e]
- ↑ Barnes PJ (2002). "Scientific rationale for inhaled combination therapy with long-acting beta2-agonists and corticosteroids.". Eur Respir J 19 (1): 182-91. PMID 11843317. [e]
- ↑ Piantanelli L, Giunta S, Basso A, Cognini G, Andreoni A, Paciaroni E (1984). "Atenolol-induced regulation of leukocyte beta 2-adrenoceptors in hypertension.". Pharmacology 29 (4): 210-4. PMID 6093157. [e]