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Nalpha-methyl Histamine and Histamine Stimulate Gastrin Release From Rabbit G-cells via Histamine H2-receptors

Nalpha-methyl Histamine and Histamine Stimulate Gastrin Release From Rabbit G-cells via Histamine H2-receptors

P W Bliss, Z V Healey, N Arebi, J Calam

Aliment Pharmacol Ther. 1999 Dec;13(12):1669-74.

PMID: 10594403

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 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.
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:
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).
Conclusion:
NalphaMH and histamine release gastrin from G-cells via H2-receptors; this might contribute to H. pylori-associated hypergastrinaemia.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248308	Anti-Histamine antibody produced in rabbit			Price

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