Biochemical Energy Backgrounds and Their Regulation in the Gastric Corpus Mucosa in Patients with Different Gastric Secretory Responses

Abstract

Many observations have been carried out to clarify the possible correlations between the gastric secretory responses and gastric fundic (corpus) mucosal biochemistry in animals. However, only a few studies have been performed in human beings (or patients) and even these gave contradictory results.

The aims of our observations were:

• 1. To evaluate the possible correlations between the gastric basal acid output (BAO) or maximal acid output (MAO) and tissue content of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenylate pool (ATP+ADP+AMP) and ‘energy charge’ [(ATP+0.5 ADP)/(ATP+ADP+AMP)] in gastric corpus mucosa of patients with ‘genuine’ peptic ulcer disease;

• 2. To identify the affinity, intrinsic activity curves and the values of pA₂, pD₂, α_ouabain and α_{pentagastгin} for the main hormones and drugs involved in the gastric inhibitory (ouabain) and stimulatory (pentagastrin, histamine) secretory responses.

The observations were carried out in patients with ‘genuine’ peptic ulcer or in their stomach (corpus) resecata obtained from surgery. The gastric basal and maximal acid output (over 1 h after 6 μg/kg sc application of pentagastrin) were measured before operation on the patients (but one week after cessation of medical treatment, except of antacids). The resecates of gastric corpus mucosa and muscular layer were obtained immediately after their resections, put into liquid nitrogen and the ATP, ADP and AMP determined from them. Adenylate pool (ATP+ADP+AMP), ratio of ATP/ADP and ‘energy charge’ [(ATP+0.5ADP)/(ATP+ADP+AMP)] were calculated. At the same time, the Mg²⁺-Na⁺-K⁺-dependent (total), only Mg²⁺-dependent and Na⁺-K⁺-dependent ATPases were prepared from the corpus mucosa and their activities expressed in µmol of P_i liberated (mg membrane protein^-1 h^-1). The affinity and intrinsic activity curves for acetylcholine, pentagastrin and histamine (and pA₂ and pD₂ values) were determined on the transformations of ATP-ADP and ATP-cAMP.

It was found that:

• 1. A positive and close correlation exists between the:

  a) BAO vs MAO (p < 0.001, n = 41); b) BAO vs. corpus mucosal (cm.) ATP (p < 0.05, n = 41); c) MAO vs. c.m. ATP (p < 0.001, n = 41); d) BAO vs. c.m. ADP (p < 0.001, n = 41); e) MAO vs. cm. ADP (p < 0.001, п = 41); f) BAO vs. cm. AMP (p < 0.05, n = 41); g) MAO vs. cm. AMP (p < 0.05, n = 41); h) BAО vs. adenylate pool (p <0.05, n=41); i) MAO vs. adenylate pool (p < 0.05, n = 41); j) BAO vs. adenine-adenosine (p < 0.05, n = 41); k) MAO vs. adenine-adenosine (p < 0.05, n = 41); I) BAO vs. ratio of ATP/ADP in the gastric corpus mucosa (p < 0.05, n = 41); m) MAO vs. ratio of ATP/ADP in the gastric corpus mucosa (p < 0.05, n = 41);n) cm. ATP vs. ADP (p < 0.001, n = 41); o) c.m. ATP vs. Na⁺-K⁺-dependent ATPase (p < 0.001, n = 41); p) c.m. ADP vs. Na⁺-K⁺-dependent ATPase (p < 0.001, п = 41);

• 2. Acetylcholine stimulates, while histamine and pentagastrin inhibit, the activity of Na⁺-K⁺-dependent ATPase;

• 3. Pentagastrin and histamine stimulate the Mg²⁺-dependent ATPase; however, Ach. had no effect on its activity;

• 4. The extent of ATP-cAMP transformation is stimulated by histamine and pentagastrin while it is inhibited by Ach.

It has been concluded that:

• 1. The gastric BAO (and MAO) secretory responses depend on the energy metabolism of the gastric corpus mucosa (ATP, ADP, AMP, adenylate pool, ratio of ATP/ADP and ‘energy charge’) and not only on the number of parietal cells;

• 2. The energy liberation from ATP (into ADP or cAMP) is regulated by acetylcholine, histamine and pentagastrin in different pathways (acetylcholine via ATP-ADP, while histamine and pentagastrin via ATP-cAMP transformation);

• 3. The ATP-ADP transformation is more sensitive than the ATP-cAMP pathway for energy liberation necessary for gastric H⁺ secretion;

• 4. The gastric H⁺ secretion is due to (a) ATP-ADP transformation and (b) ATP-cAMP transformation;

• 5. The biochemical background of energy liberation for gastric H⁺ secretion - by ATP-cAMP transformation - exists only after the inhibition of ATP-ADP transformation.

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