Bitter taste receptors effect on airway smooth muscle relaxation

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Sabra

Nat Med. 2010 Nov;16(11):1299-304. Epub 2010 Oct 24.

Bitter taste receptors on airway smooth muscle bronchodilate by localized

calcium signaling and reverse obstruction.

Deshpande DA, Wang WC, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham

JS, Liggett SB.

Department of Medicine, University of land School of Medicine, Baltimore,

land, USA.

Abstract

Bitter taste receptors (TAS2Rs) on the tongue probably evolved to evoke signals

for avoiding ingestion of plant toxins. We found expression of TAS2Rs on human

airway smooth muscle (ASM) and considered these to be avoidance receptors for

inhalants that, when activated, lead to ASM contraction and bronchospasm. TAS2R

agonists such as saccharin, chloroquine and denatonium evoked increased

intracellular calcium ([Ca(2+)](i)) in ASM in a Gβγ-, phospholipase Cβ

(PLCβ)- and inositol trisphosphate (IP(3)) receptor-dependent manner, which

would be expected to evoke contraction. Paradoxically, bitter tastants caused

relaxation of isolated ASM and dilation of airways that was threefold greater

than that elicited by β-adrenergic receptor agonists. The relaxation induced by

TAS2Rs is associated with a localized [Ca(2+)](i) response at the cell membrane,

which opens large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels, leading

to ASM membrane hyperpolarization. Inhaled bitter tastants decreased airway

obstruction in a mouse model of asthma. Given the need for efficacious

bronchodilators for treating obstructive lung diseases, this pathway can be

exploited for therapy with the thousands of known synthetic and naturally

occurring bitter tastants.

PMID: 20972434 [PubMed - in process]

Sabra Way MNIMH

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