PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 15864127

Beta2-adrenoceptor gene polymorphisms.

Otto-Erich Brodde·Kirsten Leineweber
View original source ↗Export metadata ↓

Abstract

Beta2-adrenoceptors (AR) play an important role in regulation of vascular and bronchial smooth muscle tone; functional beta2-AR, however, also exist in human heart where they can mediate positive inotropic and chronotropic effects. Recent studies have discovered that beta2-AR are polymorphic. The most common single nucleotide polymorphisms (SNPs) are: Arg16Gly, Gln27Glu, Thr164Ile in the coding region, and Arg-19Cys in the 5' upstream peptide. These SNPs affect receptor function in vitro; however, conflicting data exist on their functional relevance in vivo. This might be due to the fact that the four SNPs in the 5' upstream peptide and in the coding region, respectively, are linked and form certain haplotypes. This review gives an overview on the contribution of beta2-AR polymorphisms to cardiovascular diseases or altered drug responses. In addition, the relevance of SNPs vs. haplotypes for beta2-AR functional responsiveness is discussed.

Explore related subjects

Adrenergic beta-AgonistsGenetic Predisposition to DiseaseHaplotypesHumansLinkage DisequilibriumPolymorphism, Single NucleotideReceptors, Adrenergic, beta-2Journal ArticleResearch Support, Non-U.S. Gov'tReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Otto-Erich Brodde, Kirsten Leineweber. 2005. Beta2-adrenoceptor gene polymorphisms.. https://doi.org/10.1097/01213011-200505000-00001

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Orchidectomy increases beta-adrenoceptor activation-mediated neuronal nitric oxide and noradrenaline release in rat mesenteric artery.

BACKGROUND/AIMS: A previous study has demonstrated that endogenous male sex hormones do not alter neuronal nitric oxide (NO) release in rat mesenteric artery. However, the regulatory role of endogenous male sex hormones on noradrenaline (NA) release in rat mesenteric artery is not known. The present study was designed to analyze whether endogenous male sex hormones influence the NA release induced by electrical field stimulation (EFS), as well as the possible modification in NA and neuronal NO release by presynaptic beta-adrenoceptor activation. METHODS: For this purpose, mesenteric arteries from control and orchidectomized male Sprague-Dawley rats were used. Basal and EFS-induced neuronal NO and NA release, as well as the contractile effect induced by EFS, was measured. RESULTS: Basal and EFS-induced neuronal NO and NA release were similar in arteries from control and orchidectomized rats. The beta-adrenoceptor agonist clenbuterol did not modify EFS-induced neuronal NO and NA release in arteries from control rats. In contrast, in arteries from orchidectomized animals, clenbuterol increased both neuronal NO and NA release; this increase was prevented by incubation with the beta-adrenoceptor antagonist propranolol. However, the contractile response elicited by EFS was not modified by clenbuterol in either group of rats. CONCLUSIONS: These results show that orchidectomy does not alter the EFS-induced NA release. What is more, activation of presynaptic beta-adrenoceptors does not modify EFS-induced NA and neuronal NO release in arteries from control rats although it increases the release of both neurotransmitters in arteries from orchidectomized rats. Despite these modifications, the EFS-induced contractile response is preserved in arteries from orchidectomized rats.

Adrenergic beta-Agonists↗
PubMed2007

Effect of formoterol and salmeterol on IL-6 and IL-8 release in airway epithelial cells.

Beta(2)-adrenoceptors are widely distributed and occur on airway epithelial cells. The aim of this study was to find out whether the two long-acting beta(2)-agonists formoterol and salmeterol influence interleukin-6 (IL-6) and -8 (IL-8) release from airway epithelial cells in vitro. A549 cells and primary bronchial epithelial cells (PBEC) were stimulated with organic dust from pig barns. Non-stimulated and dust-stimulated cells were incubated for 24h with formoterol or salmeterol (10(-13)-10(-6)M) and the release of IL-6 and IL-8 into the medium was assessed by ELISA technique. Propranolol (10(-5)M) or sotalol (10(-3)M) were used to block the beta(2)-agonist mediated effects. Formoterol and salmeterol both induced enhancement of IL-6 and IL-8 release and added to the effect of organic dust. This enhanced release was blocked by a beta-blocker in PBEC but not in A549 cells. To our knowledge, this is the first time beta(2)-agonists have been shown to stimulate IL-6 release from airway epithelial cells. The results indicate different mechanisms of beta(2)-agonist action in bronchial and alveolar epithelial cells. Furthermore, our results indicate that A549 cells do not possess functional beta(2)-adrenoceptors.

Adrenergic beta-Agonists↗