Allergen and Ozone Exacerbate Serotonin-Induced Increases in Airway Smooth Muscle Contraction in a Model of Childhood Asthma

Respiration - Tập 83 Số 6 - Trang 529-542 - 2012
Brian D. Moore1, Dallas M. Hyde2, Lisa A. Miller2, Emily Wong3, Jessica Frelinger3, Edward S. Schelegle2
1Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, and Respiratory Diseases Unit, California National Primate Research Center, University of California - Davis, Davis, CA 95616-8732, USA.
2Anatomy, Physiology and Cell Biology
3UNIVERSITY OF CALIFORNIA AT DAVIS

Tóm tắt

<b><i>Background:</i></b> Serotonin (5-HT) modulates cholinergic neurotransmission and exacerbates airway smooth muscle (ASM) contraction in normal animal and nonasthmatic human tissue. Exposure to house dust mite allergen (HDMA) and ozone (O<sub>3</sub>) leads to airway hyperreactivity and 5-HT-positive cells in the airway epithelium of infant rhesus monkeys. Research shows that concomitant exposure in allergic animals has an additive effect on airway hyperreactivity. <b><i>Objectives:</i></b> In this study, the hypothesis is that the exposure of allergic infant rhesus monkeys to HDMA, O<sub>3</sub> and in combination, acting through 5-HT receptors, enhances 5-HT modulation of postganglionic cholinergic ASM contraction. <b><i>Methods:</i></b> Twenty-four HDMA-sensitized infant monkeys were split into 4 groups at the age of 1 month, and were exposed to filtered air (FA), HDMA, O<sub>3</sub> or in combination (HDMA+O<sub>3</sub>). At the age of 6 months, airway rings were harvested and postganglionic, and parasympathetic-mediated ASM contraction was evaluated using electrical-field stimulation (EFS). <b><i>Results:</i></b> 5-HT exacerbated the EFS response within all exposure groups, but had no effect in the FA group. 5-HT<sub>2</sub>, 5-HT<sub>3</sub> and 5-HT<sub>4</sub> receptor agonists exacerbated the response. 5-HT concentration-response curves performed after incubation with specific receptor antagonists confirmed the involvement of 5-HT<sub>2</sub>, 5-HT<sub>3</sub> and 5-HT<sub>4</sub> receptors. Conversely, a 5-HT<sub>1</sub> receptor agonist attenuated the tension across all groups during EFS, and in ASM contracted via exogenous acetylcholine. <b><i>Conclusions:</i></b> HDMA, O<sub>3</sub> and HDMA+O<sub>3</sub> exposure in a model of childhood allergic asthma enhances 5-HT exacerbation of EFS-induced ASM contraction through 5-HT<sub>2</sub>, 5-HT<sub>3</sub> and 5-HT<sub>4</sub> receptors. A nonneurogenic inhibitory pathway exists, unaffected by exposure, mediated by 5-HT<sub>1</sub> receptors located on ASM.

Từ khóa


Tài liệu tham khảo

10.1542%2Fpeds.2008-2233C

10.1067%2Fmai.2001.112262

10.1016%2F0091-6749%2889%2990128-0

10.1159%2F000334701

10.1016%2FS0140-6736%2802%2907597-9

10.1056%2FNEJMoa040610

10.1080%2F01926230601132030

10.1016%2FS0041-008X%2803%2900218-7

10.1016%2Fj.resp.2006.03.002

10.1016%2Fj.taap.2003.09.025

10.1111%2Fj.1365-2222.2004.02004.x

10.3109%2F09638288.2010.546936

10.1016%2FS0165-6147%2899%2901408-X

10.1006%2Fpulp.1995.1037

10.1034%2Fj.1399-3003.1999.14c26.x

10.1111%2Fj.1398-9995.1995.tb02476.x

10.1159%2F000050512

10.1159%2F000029338

10.1016%2Fj.resp.2008.06.009

10.1007%2FPL00007563

10.1159%2F000196659

10.1016%2FS1081-1206%2810%2963263-2

10.1016%2FS0009-9236%2898%2990156-4

10.1183%2F09031936.99.14510689

10.1002%2Far.20824

10.1002%2Faja.1001840104

10.1002%2Faja.1001750107

10.1378%2Fchest.101.1.2

10.1007%2FBF00824332

10.1111%2Fj.1365-2222.2003.01812.x

10.1016%2FS0002-9440%2810%2963973-9

10.1021%2Fjm00140a002

10.1016%2F0014-2999%2883%2990230-3

10.1111%2Fj.1471-4159.1986.tb04532.x

10.1111%2Fj.1469-7793.1999.0657n.x

10.1016%2F0165-1838%2895%2900054-3

10.1021%2Fjm00164a046

10.1007%2FBF00178965

10.1021%2Fjm990550b

10.1021%2Fjm960320m

10.1046%2Fj.1365-2982.2001.00295.x

10.1021%2Fjm050234z

10.3109%2F07853890008998827

10.1097%2F01.fjc.0000196238.51018.e9

10.1111%2Fj.1527-3458.2001.tb00195.x

10.1021%2Fjm00083a014

10.1038%2Fsj.bjp.0704694

10.1124%2Fmol.61.1.85

10.1016%2F0162-3109%2895%2900046-V

10.1016%2F0014-2999%2893%2990712-Q

10.1378%2Fchest.92.5.863

10.1358%2Fmf.2004.26.9.872567

10.1378%2Fchest.125.1.348

10.1080%2F15287390701598234

10.1056%2FNEJM199101313240512

10.1063%2F1.344484

10.1152%2Fajplung.00027.2006

10.1001%2Fjama.290.14.1859

10.1016%2Fj.taap.2005.12.012

10.1289%2Fehp.10497

10.1164%2Fajrccm%2F140.1.211

10.1111%2Fj.1440-1681.2005.04308.x

10.1164%2Frccm.200506-848OC

Thông tin
Thông tin xuất bản

Respiration

Tập 83 Số 6

529-542

Thông tin tác giả