Nalpha-methyl histamine and histamine stimulate gastrin release from rabbit G-cells via histamine H2-receptors.
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 Nalpha-methyl histamine (NalphaMH), which is an agonist of H3 as well as other histamine receptors. H. pylori infection also recruits mast cells, which release histamine.


OBJECTIVE
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
NalphaMH (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).


CONCLUSIONS
NalphaMH and histamine release gastrin from G-cells via H2-receptors; this might contribute to H. pylori-associated hypergastrinaemia.
Bliss
P W
PW
Department of Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Healey
Z V
ZV
Arebi
N
N
Calam
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D002744:Chlorpheniramine / Q000494:pharmacology; D017259:Dimaprit / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019863:Gastrin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism*; D006632:Histamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011706:Pyloric Antrum / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D011899:Ranitidine / Q000494:pharmacology; D011968:Receptors, Histamine / Q000502:physiology
D000911:Antibodies, Monoclonal; D005755:Gastrins; D017442:Histamine Agonists; D006633:Histamine Antagonists; D006635:Histamine H2 Antagonists; D010880:Piperidines; D011968:Receptors, Histamine; D002744:Chlorpheniramine; D006632:Histamine; D011899:Ranitidine; C052075:thioperamide; D017259:Dimaprit