Abstract Dopamine receptors are G protein-coupled receptors that are divided into two subgroups, “D 1 -like” receptors (D 1 and D 5 ) that couple to the G s protein and “D 2 -like” receptors (D 2 , D 3 , and D 4 ) that couple to G i . Although inhaled dopamine has been reported to induce bronchodilation in patients with asthma, functional expression of dopamine receptor subtypes has never been described on airway smooth muscle (ASM) cells. Acute activation of G i -coupled receptors inhibits adenylyl cyclase activity and cAMP synthesis, which classically impairs ASM relaxation. In contrast, chronic activation of G i -coupled receptors produces a paradoxical enhancement of adenylyl cyclase activity referred to as heterologous sensitization. We questioned whether the dopamine D 2 -like receptor is expressed on ASM, whether it exhibits classical G i -coupling, and whether it modulates ASM function. We detected the mRNA encoding the dopamine D 2 receptor in total RNA isolated from native human ASM and from cultured human airway smooth muscle (HASM) cells. Immunoblots identified the dopamine D 2 receptor protein in both native human and guinea pig ASM and cultured HASM cells. The dopamine D 2 receptor protein was immunohistochemically localized to both human and guinea pig ASM. Acute activation of the dopamine D 2 receptor by quinpirole inhibited forskolin-stimulated adenylyl cyclase activity in HASM cells, which was blocked by the dopamine D 2 receptor antagonist L-741626. In contrast, the chronic pretreatment (1 h) with quinpirole potentiated forskolin-stimulated adenylyl cyclase activity, which was inhibited by L-741626, the phospholipase C inhibitor U73122, or the protein kinase C inhibitor GF109203X. Quinpirole also stimulated inositol phosphate synthesis, which was inhibited by L-741626 or U73122. Chronic pretreatment (1 h) of the guinea pig tracheal rings with quinpirole significantly potentiated forskolin-induced airway relaxation, which was inhibited by L-741626. These results demonstrate that functional dopamine D 2 receptors are expressed on ASM and could be a novel therapeutic target for the relaxation of ASM. reverse transcriptase polymerase chain reaction immunoblot guinea pig organ bath Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print September 2011 , doi: 10.​1152/​ajplung.​00130.​2011 AJP - Lung Physiol February 2012 vol. 302 no. 3 L316-L324 » Abstract Free Full Text Free to you Full Text (PDF) Free to you Corrigendum All Versions of this Article: ajplung.00130.2011v1 302/3/L316 most recent Classifications Article Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Mizuta, K. Articles by Emala, C. W. PubMed PubMed citation Articles by Mizuta, K. Articles by Emala, C. W. Related Content Load related web page information Current Issue February 2012, 302 (3) Alert me to new issues of AJP - Lung Physiol About the Journal Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 1040-0605 Online ISSN: 1522-1504 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview();

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