The histamine H3 receptor agonist Nα-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. Aims-To examine the effect or 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 mu M) 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.