Aims. The aim of the present study was to compare the organoprotective (in vivo) and cytoprotective (in vitro) effects of histamine. Methods. In vivo, gastric mucosal damage was produced by intragastric (ig) administration of 1 ml 96% ethanol (EtOH) in Sprague-Dawley rats. The animals were sacrificed 1 h after EtOH administration, when the gastric mucosal damage was measured. Histamine was given subcutaneously (sc) 30 min before administration of EtOH with and without PGI2Na (5 μg/kg sc). Gastric acid secretion was also measured 1 h after pylorus ligation in control (saline-), histamine- and PGI2-treated animals. The affinity, intrinsic activity curves and the values of pD2 and pA2 were determined in EtOH-treated and in PGI2-treated animals. For the in-vitro studies, a mixed population of rat gastric mucosal cells was isolated by pronase digestion. Cells were preincubated for 60 min with histamine (10-8-10-6 mol/L) with or without PGI2Na (10-4 mol/L). At the end of this incubation period, cells were treated with 15% EtOH with or without 10-6-10-3 mol/L indomethacin (IND) for 5 min. Cell viability was tested by trypan blue exclusion test and succinic dehydrogenase activity. Results. 1. Histamine (20 mg/kg) stimulated, while PGI2 (5 μg/kg) had no effect on gastric acid secretion in rats; 2. Histamine inhibited the development of EtOH-induced gastric mucosal damage (pD2 = 4.0, pA2 = 3.75); 3. Histamine stimulated the PGI2-induced gastric cytoprotection in vivo (pD2 = 4.7, pA2 = 3.75); 4. There was no measurable acid secretion by our method in isolated cells after incubation with 10-8-10-6 mol/L histamine; 5. Histamine preincubation did not prevent the EtOH- or IND-induced cell injury. Conclusions. 1. Histamine has a protective effect in a non-acid-dependent model in vivo; 2. This organoprotection has a metabolic component; 3. The cytoprotective effect of histamine failed in vitro; 4. The mechanisms of histamine-induced organo- and cytoprotection seem to be different in rats.
- gastric cytoprotection
- gastric organoprotection
- isolated gastric mucosal cells
ASJC Scopus subject areas
- Pharmacology (medical)