Cellular Energetical Actions of "Chemical" and "Surgical" Vagotomy in Gastrointestinal Mucosal Damage and Protection: Similarities, Differences and Significance for Brain-Gut Function

Abstract

Background: The authors, as internists, registered significant difference in the long lasting actions of surgical and chemical (atropine treatment) vagotomy in patients with peptic ulcer during second half of the last century (efficency, gastric acid secretion, gastrointestinal side effects, briefly benefical and harmful actions were examined).

Aims: 1. Since the authors participated in the establishing of human clinical pharmacology in this field, they wanted to know more and more facts of the acute and chronic effects of surgical and chemical (atropine treatment) on the gastrointestinal mucosal biochemisms and their actions altered by bioactive compounds and scavengers regarding the development of gastric mucosal damage and protection.

Methods: The observations were carried out in animals under various experimental conditions (in intact, pylorus-ligated rats, in different experimental ulcer models, together with application of various mucosal protecting compounds) without and with surgical vagotomy and chemical vagotomy produced by atropine treatment.

Results: 1. No changes were obtained in the cellular energy systems (ATP, ADP, AMP, cAMP, "adenylate pool", "energy charge" [(ATP+0.5 ADP)/ (ATP+ADP+AMP)] of stomach (glandular part, forestomach) in pylorus ligated rats after surgical vagotomy in contrast to those produced by only chemical vagotomy; 2. The effects of the gastric mucosal protective compounds [atropine, cimetidine, prostaglandins, scavengers (like vitamin A, β-carotene), capsaicin] disappeared after surgical vagotomy; 3. The extents of different chemical agents induced mucosal damaging effects were enhanced by surgical vagotomy and was not altered by chemical vagotomy; 4. The existence of feedback mechanisms of pharmacological (cellular and intracellular) regulatory mechanisms between the membrane-bound ATPdependent energy systems exists in the gastric mucosa of intact animals, and after chemical vagotomy, but not after surgical vagotomy.

Conclusions: 1. Increased vagal nerve activity takes place in the gastric mucosal damage; 2 both surgical and chemical vagotomy result mucosal protective affect on the gastric mucosal in different damaging experimental models; 3. The capsaicin-induced gastric mucosal damage depends on the applied doses, presence of anatomically intact vagal nerve (but independent from the chemical vagotomy), 4. The central and pheripheral neural regulations differ during gastric mucosal damage and protection induced by drugs, bioactive compounds, scavengers.

Fig. (1)

Linkage of gastric acid output and development of gastric mucosal damage in the forestomach of pylorus-ligated rats with intact vagal nerve. Animals were sacrificed at 0, 4, 7, 14 and 24 hours after pyloric ligation. The results were expressed as ±SEM; n=15; µg, microequivalent; b.w., body weight.

Fig. (2)

The preventive effect of acute bilateral subdiaphragmatic surgical vagotomy on the gastric acid output and ulceration in plyrus-ligated rats at 0, 4, 7, 14 and 24 hrs after surgical vagotomy and pylorus ligation. The results were expressed as ±SEM; n=15; µg, microequivalent; b.w., body weight.

Fig. (3)

Changes in the cellular ATP, ADP, cAMP and AMP in the time period of first 5 hours on dependence of time after pyloric ligation. The observations were carried out from gastric fundic mucosa. The results obtained in sham-operated (normal state) were taken to be equal to 100 per cent (means±SEM) (Mozsik (2006). Molecular pharmacology and biochemistry of gastroduodenal mucosal damage and protection. In: Mózsik, G.Y. (Ed.) Discoveries in Gastroenterology (1960-2005). Akadémiai Kiadó, Budapest. pp.139-224) (with permission).

Fig. (4)

Dose-dependent inhibitory effect of atropine on the gastric acid secretion in 4 hour pylorus-ligated rats (means ±SEM). (Mózsik, Figler, Nagy, Patty, Tárnok (1981): Gastric and small intestinal energy metabolism in mucosal damage. In: Mózsik, G.Y., Hänninen O., Jávor T. (Eds.). Advances in Physiological Sciences.Vol. 29. Gastrointestinal Defence Mechanism. Pergamon Press, Oxford – Akadémiai Kiadó, Budapest.pp. 213-288) (with permission).

Fig. (5)

Atropine-induced changes in gastric H⁺ output, gastric fundic mucosal levels of ATP, ADP and AMP in 4 hours pylorus-ligated rats. The results were expressed as per cent values of obtained immediately after pylorus-ligation (=100 per cent), except of gastric H⁺ output, which was expressed also in per cent values, however obtained at 4 hours after pylorus-ligation (means ± SEM). (Mózsik, Figler, Nagy, Patty, Tárnok (1981): Gastric and small intestinal energy metabolism in mucosal damage. In: Mózsik, G.Y., Hänninen O., Jávor T. (Eds.). Advances in Physiological Sciences.Vol. 29. Gastrointestinal Defence Mechanism. Pergamon Press, Oxford – Akadémiai Kiadó, Budapest.pp. 213-288) (with permission).

Fig. (6)

Biochemical changes in the regulatory steps of cellular energy systems in the gastric fundic mucosa produced by different (cytoprotective and antisecretory) doses of atropine in 4 hours pylorus-ligated rats.

Fig. (7)

The presentation (firstly in the World) of PGI₂ gastric protective effect dipappears after bilateral surgical vagotomy in rats treated with ETOH (96 v/v) (means ±SEM) [Jávor et al., (1981) Gastric mucosal resistance to physical and chemical stress. In: Mózsik, G.Y., Hänninen O., Jávor T. (Eds.) Advances in the Physiological Sciences. Vol.29. Gastrointestinal Mucosal Defence. Pergamon Press, Oxford- Akadémiai Kiadó, Budapest. pp. 141-159] (with permission).

Fig. (8)

The effect of acute bilateral subdiaphragmatic surgical vagotomy on the development of gastric fundic mucosal lesions produced by intragastriccally administered 0.6 M HCl, 0.2 M NaOH, 25% NaCl, 96% ethanol, The results were expressed as ±SEM; n=12;** P<0.01.

Fig. (9)

The protective effect of atropine on the subcutaneously administered indomethacin-induced gastric mucoal lesions in intact and in vagotomised rats. The results were expressed as ±SEM; n=12; NS, not significant; ** P<0.01, *** P<0.001.

Fig. (10)

The effect of acute bilateral vagotomy on the number of indomethacin-induced (20 mg/kg s.c.) gastric, small intestine and large bowel lesions in the 0, 24 and 48 h experiments in rats. Each value was calculated by semiquantitative estimation using a scoring system. Data expressed as means as ±SEM; n=6. NS, not significant; * P<0.05, ** P<0.01, *** P<0.001 between the 24 and 48 h experiments without and with surgical vagotomy.

Fig. (11)

The effect of acute bilateral vagotomy on the severity of indomethacin-induced (20 mg/kg s.c.) gastric, small intestine and large bowel lesions in the 0, 24 and 48 h experiments in rats. Each value was calculated by semiquantitative estimation using a scoring system. Data expressed as means as ±SEM; n=6. NS, not significant; * P<0.05, ** P<0.01, *** P<0.001 between the 24 and 48 h experiments without and with surgical vagotomy.

Fig. (12)

The changes in gastric, small intestine and large bowel mucosal Evans Blue content (μg/g wet tissue) during the development of indomethacin-induced (20 mg/kg s.c.) mucosal damage after bilateral vagotomy in 24 and 48 hr experiments in rats. Data expressed as means as ±SEM; n=6. NS, not significant; * P<0.05, ** P<0.01, *** P<0.001 between the 24 and 48 h experiments without and with surgical vagotomy.

Fig. (13)

The changes in gastric, small intestine and large bowel juice Evans Blue content (μg) during the development of indomethacin-induced (20 mg/kg s.c.) mucosal damage after bilateral vagotomy in 24 and 48 hr experiments in rats. Data expressed as means as ±SEM; n=6. NS, not significant; * P<0.05, ** P<0.01, *** P<0.001 between the 24 and 48 h experiments without and with surgical vagotomy.