Role of taurine on acid secretion in the rat stomach

Abstract

Background: Taurine has chemical structure similar to an inhibitory neurotransmitter, γ-aminobutyric acid (GABA). Previous studies on GABA in the stomach suggest GABAergic neuron is involved in acid secretion, but the effects of taurine are poor understood.

Methods: The effects of taurine on acid secretion, signal transduction, and localization of taurinergic neurons were determined in the rat stomach using everted whole stomach, RIA kit and immunohistochemical methods.

Results: We used antibodies against taurine-synthesizing enzyme, cysteine sulfuric acid decarboxylase (CSAD), and taurine. CSAD- and taurine-positive cells were found in the muscle and mucosal layers. Distributions of CSAD- and taurine-positive cells in both mucosal and muscle layers were heterogeneous in the stomach. Taurine at 10-9~10-4 M induced acid secretion, and the maximum secretion was at 10-5 M, 1.6-fold higher than the spontaneous secretion. Taurine-induced acid secretion was completely inhibited by bicuculline and atropine but not by cimetidine, proglumide, or strychnine. Atropine and tetrodotoxin (TTX) completely inhibited the acid secretion induced by low concentrations of taurine and partially inhibited induced by high concentrations. Verapamil, a calcium blocker agent, inhibited acid output elicited by taurine. We assumed all Ca2+ channels involved in the response to these secretagogues were equally affected by verapamil. Intracellular cAMP (adenosine 3', 5'-monophosphate) in the stomach significantly increased with taurine treatment in a dose-dependent manner. High correlation (r=0.859, p < 0.001) of taurine concentrations with cAMP was observed.

Conclusions: Our results demonstrated for the first time in taurine-induced acid secretion due to increase intracellular calcium may act through the A type of GABA receptors, which are mainly located on cholinergic neurons though cAMP pathway and partially on nonneuronal cells in the rat stomach.

Figure 1

Immunohistochemical localization of cysteine sulfuric acid decarboxylase (CSAD) in the rat stomach. (A) Light micrography of a transverse section of the muscle layer showing CSAD-immunoreactive processes in the Body. (B) Light micrograph of cross section showing CSAD-positive processes in the antrum. (C) CSAD-immunoreactive cells occurred mostly in glands of the gastric mucosa. (D) CSAD-positive cell processes in the deep of mucosal layers. MP, myenteric plexus; SP, submucosa plexus. Arrowheads indicate CSAD-positive processes. Bar = 50 μm.

Figure 2

Immunohistochemical localization of taurine in the rat stomach. (A) Light micrography of cross-section showing taurine-positive processes in the antrum. (B) Light micrography of a cross-section showing taurine-immunoreactive processes in the body. (C), (D) A higher magnification of the area in (A) showing taurine-positive processes in the antrum. (E) A higher magnification of the area in (B) showing taurine-positive processes in the body. Taurine-immunoreactive cells mostly occurred in glands of the muscle layers. MM, muscularis mucosa; SM, submucosa. Arrowheads indicate taurine-positive processes. Bar = 50 μm.

Figure 3

Taurine-induced acid secretion in the absence and presence of TTX (A), atropine (B), cimetidine (C), and proglumide (D). TAU, 10^-6 M taurine alone (●, n = 6); CON, control (○, n = 6); TTX, 3 × 10^-7 M TTX alone (Δ, n = 6); TAU+TTX, 10^-6 M taurine and 3 × 10^-7 M TTX (▲, n = 6); ATR, 10^-6 M atropine alone (Δ, n = 6); TAU+ATR, 10^-6 M taurine and 10^-6 M atropine (▲, n = 6); CIM, 10^-6 M cimetidine alone (Δ, n = 6); TAU+CIM, 10^-6 M taurine and 10^-6 M cimetidine (▲, n = 6); PRO, 3 × 10^-4 M proglumide alone (Δ, n = 6); TAU+PRO, 10^-6 M taurine and 3 × 10^-4 M proglumide (▲, n = 6). Each point represents the mean ± SEM.

Figure 4

Effect of various doses of taurine-induced acid secretion in the isolated stomach. (A) Dose-dependent curve of taurine-induced acid secretion. (B) Correlation between various doses of taurine and acid secretion. Values are the mean ± SEM (n = 6).

Figure 5

Dose-dependent curve of taurine-induced acid secretion with and without atropine (A) and TTX (B). TAU, taurine alone (●, n = 6); TAU+ATR, taurine and 10^-6 M atropine; (▲, n = 6). TAU+TTX, taurine and 3 × 10^-7 M TTX; (▲, n = 6). Each point represents the mean ± SEM.

Figure 6

Effect of taurine-induced acid secretion in the absence and presence of bicuculline. (A) Acid secretion expressed as the secretory ratio was plotted against the time duration expressed in minutes. (B) Effect of 10^-6 M bicuculline on various concentrations of taurine-induced acid secretion. TAU, taurine alone (●, n = 6); CON, control (○, n = 6); TAU+BIC, taurine and 10^-6 M bicuculline (▲, n = 6); BIC, 10^-6 M bicuculline alone (Δ, n = 6). Data are the mean ± SEM.

Figure 7

Effect of taurine-induced acid secretion in the absence and presence of strychnine. Acid secretion expressed as a secretory ratio was plotted against the time duration expressed in minutes. TAU, 10^-6 M taurine (●, n = 6); CON, control (○, n = 6); STR, 10^-6 M strychnine (Δ, n = 4); TAU+STR, 10^-6 M taurine and 10^-6 M strychnine (▲, n = 4). Data are the mean ± SEM.

Figure 8

Effects of taurine-induced acid secretion in the absence and presence of verapamil. Acid secretion expressed as secretory ratio was plotted against the time duration expressed in minutes. TAU, 10^-6 M taurine (●, n = 6); TAU+VER, taurine and 10^-4 M verapamil (Δ, n = 6); TAU+VER, 10^-6 M taurine and 3 × 10^-6 M verapamil (▲, n = 6). Data are the mean ± SEM.

Figure 9

Effects of various concentrations of taurine on cyclic nucleotide levels in mucosal slices of the rat stomach. Samples were incubated at 37°C for 30 min before the addition of taurine were treated within 2 min for the production of cAMP. Each column represents the mean ± SEM of the percent basal level. * p < 0.05, significantly differs from the control (C) group (n = 5).