Alteration of airway responsiveness mediated by receptors in ovalbumin-induced asthmatic E3 rats.
OBJECTIVE
Airway hyperresponsiveness is a constant feature of asthma. The aim of the present study was to investigate airway hyperreactivity mediated by contractile and dilative receptors in an ovalbumin (OVA)-induced model of rat asthma.


METHODS
Asthmatic E3 rats were prepared by intraperitoneal injection with OVA/aluminum hydroxide and then challenged with intranasal instillation of OVA-PBS two weeks later. The myograph method was used to measure the responses of constriction and dilatation in the trachea, main bronchi and lobar bronchi.


RESULTS
In asthmatic E3 rats, beta(2) adrenoceptor-mediated relaxation of airway smooth muscle pre-contracted with 5-HT was inhibited, and there were no obvious difference in relaxation compared with normal E3 rats. Contraction of lobar bronchi mediated by 5-HT and sarafotoxin 6c was more potent than in the trachea or main bronchi. Airway contractions mediated by the endothelin (ET)(A) receptor, ET(B) receptor and M(3) muscarinic receptor were augmented, and the augmented contraction was most obvious in lobar bronchi. The order of efficacy of contraction for lobar bronchi induced by agonists was ET-1, sarafotoxin 6c>ACh>5-HT. OX8 (an antibody against CD8(+) T cells) strongly shifted and OX35 (an antibody against CD4(+) T cells) modestly shifted isoprenaline-induced concentration-relaxation curves in a nonparallel fashion to the left with an increased R(max) in asthmatic rats and sarafotoxin 6c-induced concentration-contractile curves to the right with a decreased E(max).


CONCLUSIONS
The inhibition of airway relaxation and the augmentation of contraction mediated by receptors contribute to airway hyperresponsiveness and involve CD8(+) and CD4(+) T cells.Acta Pharmacologica Sinica (2009) 30: 965-972; doi: 10.1038/aps.2009.61.
Long
Jing-Wen
JW
Department of Pharmacology, Xi'an Jiaotong University College of Medicine, Xi'an 710061, China.
Yang
Xu-Dong
XD
Cao
Lei
L
Lu
She-Min
SM
Cao
Yong-Xiao
YX
D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001993:Bronchodilator Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects* / Q000276:immunology; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012137:Respiratory System / Q000033:anatomy & histology / Q000187:drug effects / Q000276:immunology; D012701:Serotonin / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D001993:Bronchodilator Agents; D011956:Receptors, Cell Surface; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; D012701:Serotonin; D010047:Ovalbumin; D007545:Isoproterenol