• Chinese hamster ovary cells
• histamine H₂ receptors
• histamine H₃ receptors
• N-alpha-methyl-histamine
• UGT1A7
• xenobiotic metabolism
• environmental carcinogens
• colorectal cancer
• UGT1A gene locus
• allelic association

It is over 80 years since the stimulatory effect of histamine on gastric acid was reported.¹ The observation that the conventional antihistamines (subsequently shown to be H₁ antagonists) failed to block the acid stimulatory action² ultimately led to the discovery and availability of H₂ antagonists.³ These were not only effective drugs but tools to dissect acid secretory physiology, and develop our continually evolving paradigm of histamine as the major paracrine stimulant of gastric acid.⁴

In the gastric mucosa, histamine is found within enterochromaffin-like (ECL) cells and mast cells, the relative proportion of the two cell types being species and site dependent. Histamine is formed by the decarboxylation of histamine by histidine decarboxylase (HDC). After release histamine is enzymatically deactivated by two pathways. The majority is methylated onto one of the nitrogen atoms in the imidazole ring by imidazole-N-methyltransferase, and a smaller proportion is degraded by oxidative deamination to imidazole acetic acid. A further potential methylation site is on the terminal nitrogen of the side chain, producing N-alpha-methyl-histamine (NAMH). In 1935, soon after it was first chemically synthesised, NAMH was shown to be a potent stimulant of canine acid secretion.⁵ NAMH …