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ß-Phenylethylamine (ß-PEA) is a trace amine with chemical proximity to biogenic amines and amphetamines. It is an endogenous agonist of trace amine-associated receptors (TAARs) that acts as a neuromodulator of classic neurotransmitters in the central nervous system. At high concentrations, ß-PEA contracts smooth muscle, and a role for TAARs in these responses has been postulated. The high dietary intake of trace amines has been associated with such symptoms as hypertension and migraine, especially after the intake of foods containing such compounds. In gastrointestinal tissues, TAAR expression was reported, although the effect of ß-PEA on gastric contractile behaviour is unknown. Here, isolated strips that were obtained from the rat gastric fundus were stimulated with high micromolar concentrations of ß-PEA. Under resting tonus, ß-PEA induced contractions. In contrast, when the strips were previously contracted with KCl, a relaxant response to ß-PEA was observed. The contractile effect of ß-PEA was inhibited by 5-hydroxytryptamine (5-HT) receptor antagonists (i.e., cyproheptadine and ketanserin) but not by the TAAR1 antagonist EPPTB. In gastric fundus strips that were previously contracted with 80 mmol/L KCl, the relaxant effect of ß-PEA intensified in the presence of 5-HT receptor antagonists, which was inhibited by EPPTB and the adenylyl cyclase inhibitor MDL-12,330A. The guanylyl cyclase inhibitor ODQ did not alter the relaxant effects of ß-PEA. In conclusion, ß-PEA exerted dual contractile and relaxant effects on rat gastric fundus. The contractile effect appeared to involve the recruitment of 5-HT receptors, and the relaxant effect of ß-PEA on KCl-elicited contractions likely involved TAAR1 .

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NEW FINDINGS: 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 Gq/11 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 Ca2+ 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 Ca2+ -free conditions, repeated contractions that were induced by carbachol progressively decreased, with no influence of extracellular pH. In fundus strips, CaCl2 -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 CaCl2 in the presence of KCl did not change with pH acidification. In Ca2+ store-depleted preparations that were treated with thapsigargin, the contractions that were induced by extracellular Ca2+ 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 Ca2+ 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 Gq/11 protein signalling pathway, whereas electromechanical coupling remained functionally preserved.

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In rat stomach fundus, contractions induced by Ca2+ (1.8 mM) were strikingly potentiated by thapsigargin. This potentiation was partially inhibited by the blockers of Ca2+ release activated channels (CRACs), miconazole and SK&F96365 ([1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole, HCL]) and slightly blocked by the antagonist of calcium voltage-operated channels (VOCs), isradipine. In dissociated cells in a 0Ca solution, thapsigargin potentiated the increase in intracellular calcium after reintroduction of Ca2+. This potentiation was partially reduced by the CRAC blockers, but not by the VOC blockers. This data suggests that calcium influx increased due to the depletion of intracellular calcium by thapsigargin and that this influx occurs predominantly through CRACs.

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It is generally agreed that Helicobacter pylori (Hp) plays a key role in alterating regulatory factors affecting cellular proliferation during the disease process. During chronic superficial gastritis there is, in case of moderate/severe activity, a foveolar-superficial expansion of immature muco-peptic cells. In the present experience this phenomenon has been evaluated in the surrounding areas of 22 body-fundic gastric ulcer (BFGU). The 72.7% of BFGU were Hp positive. The expansion was detectable in 68.7% of Hp positive BFGU. The expansion process involves the substitution of mature cells with immature one determining a reduction of the efficacy of the mucosa barrier in association with an increment of aggressive factors (mucosal pepsins). This phenomenon in relation with host genetic susceptibility may favor peptic ulcer.

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It is generally agreed that Helicobacter pylori (Hp) plays a key role in alterating regulatory factors affecting cellular proliferation during the disease process. During chronic superficial gastritis there is, in case of moderate/severe activity, a foveolar-superficial expansion of immature muco-peptic cells. In the present experience this phenomenon has been evaluated in the surrounding areas of 22 body-fundic gastric ulcer (BFGU). The 72.7 percent of BFGU were Hp positive. The expansion was detectable in 68.7 percent of Hp positive BFGU. The expansion process involves the substitution of mature cells with immature one determining a reduction of the efficacy of the mucosa barrier in association with an increment of aggresive factors (mucosal pepsins). This phenomenon in relation with host genetic susceptibility may favor peptic ulcer. (AU)

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It is generally agreed that Helicobacter pylori (Hp) plays a key role in alterating regulatory factors affecting cellular proliferation during the disease process. During chronic superficial gastritis there is, in case of moderate/severe activity, a foveolar-superficial expansion of immature muco-peptic cells. In the present experience this phenomenon has been evaluated in the surrounding areas of 22 body-fundic gastric ulcer (BFGU). The 72.7 percent of BFGU were Hp positive. The expansion was detectable in 68.7 percent of Hp positive BFGU. The expansion process involves the substitution of mature cells with immature one determining a reduction of the efficacy of the mucosa barrier in association with an increment of aggresive factors (mucosal pepsins). This phenomenon in relation with host genetic susceptibility may favor peptic ulcer.

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