title: R- and S-terbutaline activate large conductance and Ca2+dependent K+(BKCa) channel through interacting with β2and M receptor respectively.
abstract: This study investigated the effect of the β2receptor agonist terbutaline on the single channel activity of BKCachannel. The effects of racemate and two isomers of terbutaline were all assessed. β2adrenoceptors were stably overexpressed on HEK293 cells by lentiviral transduction method and chicken BKCachannels were transiently expressed on normal HEK293 cell line or HEK293 cells overexpressing β2receptors. Data showed that terbutaline significantly increased the single channel open probability of BKCachannel within 10min. The channel activating effects of terbutaline are stereoselective and mainly stay with the R-enantiomers. The opening probability of BKCachannel at 10min after drug application normalized to that just before drug application (Po10/Po0s) for R- and S-terbutaline were 7.85±3.20 and 1.06±0.45 respectively at 1μM concentration, corresponding to 28.37±9.96 and 2.68±1.09 at the higher concentration of 10μM. ICI 118551 blocked the effect of R- but not S-terbutaline (10μM), whereas atropine blocked the channel activating effects of S-terbutaline of higher concentration. In addition, the muscarinic receptor agonist carbachol increased the BKCachannel activity in an atropine-sensitive manner as an positive control experiment, which indicate the involvement of M receptor in the channel activating effect of S-terbutaline.
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, South China University of Technology, Guangzhou 510006, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Fan
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.
authors.forename: Nanying
authors.initials: N
authors.lastname: Lv
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, South China University of Technology, Guangzhou 510006, China.
authors.forename: Yanrui
authors.initials: Y
authors.lastname: Ye
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China; Institute of Biomedical & Pharmaceutical Sciences, Guangdong University of Technology, NO. 100 Waihuan Xi Road, Guangzhou 510006, Higer Education Mega Center, China; Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, South China University of Technology, Guangzhou 510006, China. Electronic address: went@gdut.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002645:Chickens; D015870:Gene Expression; D005822:Genetic Vectors / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000235:genetics / Q000378:metabolism*; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D013237:Stereoisomerism; D013726:Terbutaline / Q000494:pharmacology*; D019076:Transgenes
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D011976:Receptors, Muscarinic; C026777:ICI 118551; D001285:Atropine; D002217:Carbachol; D013726:Terbutaline
keywords: BK(Ca) channel; Enantiomer; Muscarinic receptor; Terbutaline; β(2)-adrenoceptor