ArticleClinical and experimental pharmacology & physiology2022
Histamine via histamine H1 receptor enhances the muscarinic receptor-induced calcium response to acetylcholine in an enterochromaffin cell model.
Article in Clinical and experimental pharmacology & physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 4 citations in OpenAlex.
- Activation of peripheral muscarinic receptors rescues depressive-like behaviors via gut-brain-axis, involving parasympathetic excitation.Acta pharmacologica Sinica · 2026Article
- Protease-Activated Receptor 2 Activation Provokes an Increase in Intracellular Calcium and Serotonin Secretion in a Human Enteroendocrine Cell Line.Cell biochemistry and function · 2025Article
- Histamine via histamine H1 receptor enhances the muscarinic receptor-induced calcium response to acetylcholine in an enterochromaffin cell model.Clinical and experimental pharmacology & physiology · 2022Article
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
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Abstract
As a prerequisite for serotonin secretion, the P-STS ileal enterochromaffin cell line responds to acetylcholine (ACh) stimulation with an increase in intracellular calcium mediated by the muscarinic ACh receptor M3 (M3R). Histamine increases intracellular calcium via histamine H1 receptor (H1R) in P-STS cells and pre-incubation with histamine specifically augments the response to ACh but not to epinephrine or nicotine. We aimed to elucidate whether histamine receptors are involved in this synergism. Astonishingly, HEK-293 T cells-known to express M3R, but only a very low amount of histamine receptor messenger RNA-showed a similar enhancement of the calcium response to ACh by pre-incubation with histamine. Despite the much lower level of H1R protein detected in HEK-293 T cells as compared to P-STS cells, in both cell lines pre-treatment with H1R antagonists inhibited the synergism between histamine and ACh. No indication for an involvement of histamine H2 or H4 receptors in the synergism was found. Furthermore, pre-incubation with the cAMP-inducing compound forskolin had no influence on the intracellular calcium response to ACh. Serotonin secretion from P-STS cells was increased after challenge with ACh and histamine added simultaneously compared to ACh alone, suggesting that histamine increases ACh-induced serotonin secretion from enterochromaffin cells. In conclusion, our data suggest that histamine enhances the M3R-mediated intracellular calcium response to ACh via activation of H1R. This probably increases serotonin secretion from enterochromaffin cells and thereby affects intestinal motility in histamine intolerance, food allergies and irritable bowel syndrome.
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