Quercetin relaxes human gastric smooth muscles directly through ATP-sensitive potassium channels and not depending on the nitric oxide pathway

Abstract

Background: Quercetin has recently become a remarkably popular subject of research due to its broad beneficial pharmacological properties. The goal of our study was to observe its effects on contractility of human gastric smooth muscles in reference to the NO pathway and direct influence of potassium channels.

Methods: Tissues were obtained from patients undergoing sleeve gastrectomy due to morbid obesity (n = 10 aged 24-56; BMI 47.16 ± 1.84). The following parameters were evaluated in the recordings: area under the curve (AUC), average baseline muscle tone, and relative change in muscle contraction.

Key results: Quercetin induced noticeable, dose-dependent relaxation of the carbachol treated gastric strips. The substantial effect was noted at concentrations higher than 10^-7 mol/L and maximal at 10^-4 mol/L (81.82 ± 3.32%; n = 10; p < 0.0001) of the control. Neither NOS blockers nor guanylyl cyclase blockers had inhibitory effects on the relaxation of strips induced by examined polyphenol. Glibenclamide inhibited the relaxing effect of quercetin, significant at concentrations higher than 5⋅10^-5 mol/L. Preincubation with charybdotoxin or apamin extended the relaxing effect of quercetin (from 10^-6 mol/L). Tamoxifen, in turn, significantly increased muscle relaxation at all quercetin concentrations.

Conclusions & inferences: In conclusion, the current study was the first to show that quercetin-induced relaxation of human gastric smooth muscle occurs directly through K⁺_ATP channels and independently to NO pathways. The present results suggest that quercetin is a potential nutraceutical in the treatment of functional gastrointestinal dyspepsia and other minor gastric muscle motility disturbance.

Keywords: gastric motility; gastric smooth muscles; nitric oxide; potassium channels; quercetin.

FIGURE 1

A typical recording of carbachol‐induced contractile activity of the gastric strips and the effect of cumulatively administered quercetin range 10⁻⁷–10⁻⁴ mol/L. (A)—control; (B)—quercetin after preincubation with L‐NNA (10⁻⁵ mol/L); (C)—quercetin after preincubation with apamin (10⁻⁶ mol/L)

FIGURE 2

An original tracing of the effect of cumulatively administered quercetin range 10⁻⁷–10⁻⁴ mol/L on carbachol‐induced contractile activity of the gastric strips (A)—quercetin alone; after preincubation with glibenclamide (B)—10⁻⁶ mol/L, (C)—10⁻⁵ mol/L

FIGURE 3

An original tracing of the effect of cumulatively administered pinacidil range 10⁻⁷–10⁻⁴ mol/L on carbachol‐induced contractile activity of the gastric strips (A)—pinacidil alone; after preincubation with glibenclamide (B)—10⁻⁶ mol/L, (C)—10⁻⁵ mol/L

FIGURE 4

Effects of quercetin after preincubation with (A, D)—L‐NNA, L‐NAME, ODQ and cystamine; (B, E)—CTX or apamin; (C, F) tamoxifen on the gastric strips, as measured by AUC (A, B or D) and basal tension (D, E or F). Each point represents mean ±SEM of values obtained from individual gastric strips (n = 10) from different patients. Contractions of the gastric strips before quercetin were treated as controls

FIGURE 5

Effects of quercetin after preincubation with glibenclamide (A, C)—10⁻⁶ mol/L, (B, D)—10⁻⁵ mol/L on the gastric strips, as measured by AUC (A or B) and basal tension (C or D). Each point represents mean ±SEM of values obtained from individual gastric strips (n = 10) from different patients. Contractions of the gastric strips before quercetin were treated as controls

FIGURE 6

Effects of NOS inhibitors—L‐NNA, L‐NAME; a sGC inhibitor—ODQ or cystamine;; a BK_Ca channel blocker—CTX; a SK_Ca channel blocker—apamin ADRB or an estrogen receptor blocker—tamoxifen; an ATP‐sensitive K⁺ blocker—glibenclamide 10⁻⁶ mol/L and 10⁻⁵ mol/L as measured by AUC (A) and basal tension (B) on the carbachol‐induced contractions in strips of gastric muscles. Carbachol‐induced contractile activity was treated as control values. The values are mean ±SEM of n (n = 10) individual myometrial strips from different patients. Asterisk indicates values significantly different from a control.^* p < 0.05; *** p < 0.001