The histamine H3 receptor agonist N alpha-methylhistamine produced by Helicobacter pylori does not alter somatostatin release from cultured rabbit fundic D-cells.
BACKGROUND
The mechanisms underlying the suppression of somatostatin dependent reflexes in Helicobacter pylori infection are not fully determined. The H pylori product N alpha-methylhistamine and inflammatory mediators such as tumour necrosis factor-alpha (TNF-alpha) may be responsible for the alterations in somatostatin release.


OBJECTIVE
To examine the effect of N alpha-methylhistamine on somatostatin release from cultured somatostatin-secreting D-cells.


METHODS
Rabbit fundic D-cells were obtained by collagenase-EDTA digestion and enriched by centrifugal elutriation and cultured for 40 hours. The effects of N alpha-methylhistamine on somatostatin release soon after stimulation (two hours) and after more prolonged exposure (24 hours) were assessed.


RESULTS
N alpha-Methylhistamine (1 nM-1 microM) had no effect on basal or carbachol or adrenaline stimulated release over two hours. Similarly with prolonged exposure no effect on somatostatin cell content or release was identified. In contrast, TNF-alpha (24 hours) led to a dose dependent fall in both somatostatin content and release.


CONCLUSIONS
N alpha-Methylhistamine had no direct inhibitory effects on D-cells, but TNF-alpha both significantly reduced the cellular content and inhibited release. Inflammatory cytokines, rather than N alpha-methylhistamine, are therefore likely to be responsible for directly inhibiting D-cell function in H pylori infection.
Beales
I L
IL
Department of Gastroenterology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Calam
J
J
D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori / Q000378:metabolism*; D008761:Methylhistamines / Q000494:pharmacology*; D011817:Rabbits; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism*; D019864:Somatostatin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D008761:Methylhistamines; D018100:Receptors, Histamine H3; D014409:Tumor Necrosis Factor-alpha; D013004:Somatostatin; C048140:N-methylhistamine