Extracellular acidosis selectively inhibits pharmacomechanical coupling induced by carbachol in strips of rat gastric fundus

Abstract

What is the central question of this study? Acute acidosis that results from short-term exercise is involved in delayed gastric emptying in rats and the lower responsiveness of gastric fundus strips to carbachol. Does extracellular acidosis decrease responsiveness to carbachol in tissues of sedentary rats? How? What is the main finding and its importance? Extracellular acidosis inhibits cholinergic signalling in the rat gastric fundus by selectively influencing the G protein signalling pathway. Acute acidosis that results from short-term exercise delays gastric emptying in rats and decreases the responsiveness to carbachol in gastric fundus strips. The regulation of cytosolic Ca concentrations appears to be a mechanism of action of acidosis. The present study investigated the way in which acidosis interferes with gastric smooth muscle contractions. Rat gastric fundus isolated strips at pH 6.0 presented a lower magnitude of carbachol-induced contractions compared with preparations at pH 7.4. This lower magnitude was absent in carbachol-stimulated duodenum and KCl-stimulated gastric fundus strips. In Ca -free conditions, repeated contractions that were induced by carbachol progressively decreased, with no influence of extracellular pH. In fundus strips, CaCl -induced contractions were lower at pH 6.0 than at pH 7.4 but only when stimulated in the combined presence of carbachol and verapamil. In contrast, verapamil-sensitive contractions that were induced by CaCl in the presence of KCl did not change with pH acidification. In Ca store-depleted preparations that were treated with thapsigargin, the contractions that were induced by extracellular Ca restoration were smaller at pH 6.0 than at pH 7.4, but relaxation that was induced by SKF-96365 (an inhibitor of store-operated Ca entry) was unaltered by extracellular acidification. At pH 6.0, the phospholipase C inhibitor U-73122 relaxed carbachol-induced contractions less than at pH 7.4, and this phenomenon was absent in tissue that was treated with the RhoA kinase blocker Y-27632. Thus, extracellular acidosis inhibited pharmacomechanical coupling in gastric fundus by selectively inhibiting the G protein signalling pathway, whereas electromechanical coupling remained functionally preserved.

Alanyl-glutamine protects the intestinal barrier function in trained rats against the impact of acute exhaustive exercise

“…In this sense, we recently reported that acute exercise delays the gastric emptying rate in rats, a phenomenon prevented by bicarbonate treatment. In addition, extracellular acidosis in vitro inhibits cholinergic neurotransmission in the rat gastric fundus by selectively influencing the Gq/11 protein-signaling pathway (22,23). Now, we report for the first time the morphofunctional modifications in the intestinal barrier, such as increased intestinal permeability associated with changes in the transcription of a tight junction (claudin-2) in a physically exhaustive test, which was prevented by AG treatment.…”

Moderate Physical Exercise Activates ATR2 Receptors, Improving Inflammation and Oxidative Stress in the Duodenum of 2K1C Hypertensive Rats

“…Carbachol (CCh) is a cholinergic agonist that binds to muscarinic receptors coupled to the G protein, specifically Gq/11, which releases calcium and consequently elicits smooth muscle contraction (Silva et al, 2014;Oliveira et al, 2017). Regarding the CCh responsiveness protocol of gastrointestinal tissues, there was a shift to the right of the contractility curve of the duodenum strips in 2K1C rats, indicating reduced responsiveness to the CCh cholinergic agonist.…”

Acute exercise inhibits gastric emptying of liquids in rats: influence of the NO-cGMP pathway

“…In addition, we recently showed that pharmacomechanical stimulation induced by cholinergic signaling through muscarinic receptors is affected by extracellular acidosis in isolated preparations of rat gastric fundus (40). This phenomenon could also be involved in the exercise-induced gastric emptying delay in rats (i.e., a condition that causes lactate-derived extracellular acidification) (7).…”