Dataset Information

Bitter tasting compounds dilate airways by inhibiting airway smooth muscle calcium oscillations and calcium sensitivity.

ABSTRACT:

Background and purpose

While selective, bitter tasting, TAS2R agonists can relax agonist-contracted airway smooth muscle (ASM), their mechanism of action is unclear. However, ASM contraction is regulated by Ca²⁺ signalling and Ca²⁺ sensitivity. We have therefore investigated how the TAS2R10 agonists chloroquine, quinine and denotonium regulate contractile agonist-induced Ca²⁺ signalling and sensitivity.

Experimental approach

Airways in mouse lung slices were contracted with either methacholine (MCh) or 5HT and bronchodilation assessed using phase-contrast microscopy. Ca²⁺ signalling was measured with 2-photon fluorescence microscopy of ASM cells loaded with Oregon Green, a Ca²⁺-sensitive indicator (with or without caged-IP₃). Effects on Ca²⁺ sensitivity were assessed on lung slices treated with caffeine and ryanodine to permeabilize ASM cells to Ca²⁺ .

Key results

The TAS2R10 agonists dilated airways constricted by either MCh or 5HT, accompanied by inhibition of agonist-induced Ca²⁺ oscillations. However, in non-contracted airways, TAS2R10 agonists, at concentrations that maximally dilated constricted airways, did not evoke Ca²⁺ signals in ASM cells. Ca²⁺ increases mediated by the photolysis of caged-IP₃ were also attenuated by chloroquine, quinine and denotonium. In Ca²⁺-permeabilized ASM cells, the TAS2R10 agonists dilated MCh- and 5HT-constricted airways.

Conclusions and implications

TAS2R10 agonists reversed bronchoconstriction by inhibiting agonist-induced Ca²⁺ oscillations while simultaneously reducing the Ca²⁺ sensitivity of ASM cells. Reduction of Ca²⁺ oscillations may be due to inhibition of Ca²⁺ release through IP₃ receptors. Further characterization of bronchodilatory TAS2R agonists may lead to the development of novel therapies for the treatment of bronchoconstrictive conditions.

SUBMITTER: Tan X

PROVIDER: S-EPMC3969078 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Publications

Bitter tasting compounds dilate airways by inhibiting airway smooth muscle calcium oscillations and calcium sensitivity.

Tan Xiahui X Sanderson Michael J MJ

British journal of pharmacology 20140201 3

<h4>Background and purpose</h4>While selective, bitter tasting, TAS2R agonists can relax agonist-contracted airway smooth muscle (ASM), their mechanism of action is unclear. However, ASM contraction is regulated by Ca²⁺ signalling and Ca²⁺ sensitivity. We have therefore investigated how the TAS2R10 agonists chloroquine, quinine and denotonium regulate contractile agonist-induced Ca²⁺ signalling and sensitivity.<h4>Experimental approach</h4>Airways in mouse lung slices were contracted with either ...[more]

PMID: 24117140

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Project description:BackgroundInfants are born with the biological predisposition to reject bitterness. Dark green vegetables contain essential nutrients but also bitter compounds, making them more difficult to like.ObjectiveThe Good Tastes Study was designed to determine whether reducing bitterness by adding small amounts of sugar or salt would alter infant acceptance of kale purées.MethodsCaregivers (n = 106, 94% mothers, 82% Non-Hispanic White) and children (53% male, aged 6-24 mo) participated in a videorecorded laboratory visit during which infants were offered 4 versions of puréed kale: plain, 1.2% or 1.8% added sugar, or 0.2% added salt. Caregivers rated their children's liking for each kale version. Videos were coded for the number of tastes accepted and for children's behaviors and acceptance of each kale version. A multilevel ordered logistic model was fit for the number of accepted tastes and caregiver ratings of child liking of kale versions with age, breastfeeding history, order effects, and kale version as predictors.ResultsInfants 6 to <12 mo accepted more tastes (b = 2.911, P < 0.001) and were rated by caregivers as liking the kale more than older toddlers (≥18 mo; b = 1.874, P = 0.014). The plain kale was more likely to be accepted (P < 0.001); also, the first version offered was more likely to be rejected (b = -0.586, P < 0.007). Older infants (≥18 mo) exhibited more avoidant behaviors (b = 1.279, P < 0.001), more playing (b = 2.918, P < 0.001), and more self-feeding (b = 1.786, P = 0.005) than younger infants (6 to <12 mo). Children who were reported to have been breastfed more in the last 7 d were more likely to self-feed (b = 0.246, P < 0.001) and play with food (b = 0.207, P < 0.005).ConclusionsOur findings support that there may be a sensitive period, during the early phase of complementary feeding, to improve success of introducing a novel, bitter, more difficult-to-like food. When low levels of sugar or salt were added, no advantage of bitterness reduction was observed. This study has been registered with ClinicalTrials.gov as NCT04549233.

Dataset Information

Bitter tasting compounds dilate airways by inhibiting airway smooth muscle calcium oscillations and calcium sensitivity.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Publications

Bitter tasting compounds dilate airways by inhibiting airway smooth muscle calcium oscillations and calcium sensitivity.

Similar Datasets

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