Increased responsiveness to 5‐hydroxytryptamine after antigenic challenge is inhibited by nifedipine and niflumic acid in rat trachea in vitro*

Abstract

Antigenic challenge often induces hyperreactivity in asthmatic airway, although the precise mechanism(s) underlying this increased responsiveness is not entirely known. Tracheae obtained from ovalbumin (OVA)-sensitized saline- or OVA-challenged rats were placed in 10 mL bath chambers for isometric recording of 5-hydroxytryptamine (5-HT)-induced contractions. 5-Hydroxytryptamine induced a stronger contraction compared with control in antigen-challenged trachea under normal or Ca2+-free conditions. In tracheae pretreated with the L-type Ca2+ channel blocker nifedipine (10(-6) mol/L) or the Ca2+-activated Cl- channel blocker niflumic acid (10(-4) mol/L), this hyperresponsiveness was not developed in either normal or Ca2+-free medium. The increased contractile response to 5-HT in allergic rat isolated trachea may be related to a greater ionic (Ca2+ and Cl-) channel involvement.

Inhibitory effects of a standardized extract of Justicia pectoralis in an experimental rat model of airway hyper-responsiveness

“…In contrast, the best‐documented KCl‐elicited route of Ca 2+ entry into airway smooth muscle cells is via dihydropyridine‐sensitive voltage‐operated Ca 2+ channels . We have already showed that antigen challenge with OVA increases contractile response in isolated trachea of allergic rats by a supposedly greater ionic Ca 2+ channel involvement . In the present study, the hyper‐responsive behaviour of OVA‐challenged tracheal rings is compatible with an increased influx of receptor‐ or voltage‐operated pathways, both putatively inhibited by the extract of J. pectoralis and coumarin, which clearly shifted to the right the Ca 2+ ‐induced concentration–effect curve in OVA‐challenged preparations maintained in the presence of either ACh or KCl, respectively.…”

Essential oil of Pterodon polygalaeflorus inhibits electromechanical coupling on rat isolated trachea

“…This Ca 2+ influx is due to either opening of VOCCs, since the activation of 5-HT receptors may induce cell depolarization (Coburn and Yamaguchi, 1977) or supplied by a voltage-independent pathway, such as ROCC activation. Teixeira et al (2000) and Moura et al (2005) demonstrate that nifedipine, a Ca 2+ channel blocker, reduces only partially the 5-HT-induced contractions on rat airway smooth muscle. Thus, it is reasonable to conclude that EOPP was more potent against K + -than 5-HT-induced contractions because K + -induced contractions involves only VOCC activation.…”

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

“…There is also the possibility of partial activation of multiple receptor subtypes by any one agonist, especially at higher concentrations. There is evidence that 5-HT may directly induce the contraction of smooth muscle [19,20,79]. When higher concentrations of 5-HT and some of the agonists were added, sporadic baseline shifts in tension were recorded.…”