Nα‐methyl histamine and histamine stimulate gastrin release from rabbit G‐cells via histamine H2‐receptors

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Abstract
Background: Gastrin release by Helicobacter pylori may be an important step in the pathway leading to duodenal ulceration. A histamine H3‐receptor agonist was found to release gastrin from antral mucosal fragments; this was interpreted as being due to suppression of somatostatin release. H. pylori is reported to produce Nα‐methyl histamine (NαMH), which is an agonist of H3 as well as other histamine receptors. H. pylori infection also recruits mast cells, which release histamine. Aim: To determine the direct effects of histamine receptor agonists on isolated gastrin cells. Methods: Rabbit G‐cells were prepared by countercurrent elutriation and cultured on 24‐well plates. Results: NαMH (10–6–10–4 M) caused a dose‐dependent increase in gastrin release from a basal level of 2.3 ± 0.2% total cell content (TCC; mean ± S.E.M.) to a maximum of 5.1 ± 0.7%, an increase of 117% (P < 0.005) above basal. This was abolished by the H2‐antagonist ranitidine (10–5 M), but not by immunoblockade with anti‐somatostatin antibody, the H1‐antagonist chlorpheniramine (10–5 M) or the H3‐antagonist thioperamide (10–4 M). The histamine H2‐receptor agonist dimaprit (10–6–10–4 M) increased gastrin release from 2.4 ± 0.2% to 3.6 ± 0.2% TCC (P < 0.001). Gastrin release was also stimulated by histamine (10–7–10–4 M) from a basal value of 3.0 ± 0.3% to 5.4 ± 0.5% TCC (P < 0.001). This also was inhibited by ranitidine (10–5 M) (P < 0.01). Conclusion: NαMH and histamine release gastrin from G‐cells via H2‐receptors; this might contribute to H. pylori‐associated hypergastrinaemia.