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. 1998 Aug;43(2):176–181. doi: 10.1136/gut.43.2.176

The histamine H3 receptor agonist N -methylhistamine produced by Helicobacter pylori does not alter somatostatin release from cultured rabbit fundic D-cells

I Beales 1, J Calam 1
PMCID: PMC1727208  PMID: 10189840

Abstract

Background—The mechanisms underlying the suppression of somatostatin dependent reflexes in Helicobacter pylori infection are not fully determined. The H pylori product N -methylhistamine and inflammatory mediators such as tumour necrosis factor-α (TNF-α) may be responsible for the alterations in somatostatin release. 
Aims—To examine the effect of N -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 -methylhistamine on somatostatin release soon after stimulation (two hours) and after more prolonged exposure (24 hours) were assessed. 
Results—N -Methylhistamine (1 nM-1 µM) 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-α (24 hours) led to a dose dependent fall in both somatostatin content and release. 
Conclusions—N -Methylhistamine had no direct inhibitory effects on D-cells, but TNF-α both significantly reduced the cellular content and inhibited release. Inflammatory cytokines, rather than N -methylhistamine, are therefore likely to be responsible for directly inhibiting D-cell function in H pylori infection. 



Keywords: D-cell; Helicobacter pylori; H3 receptor; N -methylhistamine; somatostatin; tumour necrosis factor α

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Figure 1 .

Figure 1

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Effect of N -methylhistamine on somatostatin release from cultured D-cells. Somatostatin release over two hours in the presence of increasing concentrations of N -methylhistamine was measured in the basal state or when cells were co-stimulated with cholecystokinin 10 nM (CCK) or adrenaline (EPI) and isobutylmethyxanthine (IBMX) both 100 µM. Values are mean (SEM), n = 3. 


Figure 2 .

Figure 2

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Effect of carbachol (10 µM) and octreotide (10 nM) on somatostatin release stimulated by cholecystokinin (CCK; 10 nM) and adrenaline with isobutylmethylxanthine (both 100 µM; EPI). Values are mean (SEM), n = 3. *p<0.05 compared with the stimulated somatostatin release. 


Figure 3 .

Figure 3

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Effect of combining H1 receptor antagonism (chlorpheniramine 10 µM), H2 receptor antagonism (ranitidine 10 µM), and the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX, 100 µM) on somatostatin release from D-cells stimulated with N -methylhistamine (100 nM) (N MH). Values are mean (SEM), n = 3. 


Figure 4 .

Figure 4

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Effect of 24 hours preincubation with tumour necrosis factor-α (TNF-α) (A) and N -methylhistamine (B) on the somatostatin content of cultured D-cells. Results are expressed as percentage of control cells on the same culture plate. Values are mean (SEM), n = 5. *p<0.05 compared with control (no TNF-α). 


Figure 5 .

Figure 5

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Effect of 24 hours preincubation with tumour necrosis factor (TNF-α) (A) and N -methylhistamine (B) on the somatostatin release from cultured D-cells in response to cholecystokinin 10 nM. Results are expressed as percentage of control cells on the same culture plate. Values are mean (SEM), n = 5. *p<0.05, **p<0.01 compared with controls (no TNF-α). 


Figure 6 .

Figure 6

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Effect of N -methylhistamine and tumour necrosis factor-α (TNF-α) on cell numbers and viability. After 24 hours incubation in test agents, viable cell numbers were measured by MTT assay. Cell numbers were quantified by measuring the optical density at 550 nm of the extracted formazan product. Values are mean (SEM), n = 3. 


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