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Nα‐methyl histamine and histamine stimulate gastrin release from rabbit G‐cells via histamine H 2 ‐receptors
Author(s) -
Philip Bliss,
Zoe V. Healey,
Naila Arebi,
John Calam
Publication year - 1999
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.1999.00649.x
Subject(s) - dimaprit , histamine , gastrin , thioperamide , medicine , endocrinology , agonist , histamine h2 receptor , g cell , somatostatin , histamine h4 receptor , chemistry , histamine receptor , receptor , antagonist , histamine h3 receptor , secretion
Background: Gastrin release by Helicobacter pylori may be an important step in the pathway leading to duodenal ulceration. A histamine H 3 ‐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 H 3 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 H 2 ‐antagonist ranitidine (10 –5 M ), but not by immunoblockade with anti‐somatostatin antibody, the H 1 ‐antagonist chlorpheniramine (10 –5 M ) or the H 3 ‐antagonist thioperamide (10 –4 M ). The histamine H 2 ‐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 H 2 ‐receptors; this might contribute to H. pylori ‐associated hypergastrinaemia.