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Lack of evidence for histamine H3 receptor function in rat ileum and human colon
M Hemedah1, R Loiacono, I M Coupar
1Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, Parkville, Australia.
Abstract:
The effects of histamine and the more selective H3 receptor agonist (R)alpha-methylhistamine were investigated on contractile responses produced by electrical stimulation of the longitudinal and circular muscles of the rat ileum and the circular muscle of the human colon. Histamine (0.1-3.0 microM) and (R)alpha-methylhistamine (0.1-3.0 microM) had no significant effect (P>0.05) on cholinergic nerve stimulation of either the longitudinal or circular muscle of the rat ileum nor the circular muscle of the human colon. Substance P (1 microM) and nicotine (0.1 microM), which both produce a contraction via activation of cholinergic nerves, were also unaffected by histamine (1 microM and 10 microM) or (R)alpha-methylhistamine (1 microM and 10 microM), in either tissue. Preliminary studies using in situ hybridisation histochemistry (ISHH) were performed in rat brain and ileum in an attempt to identify H3 receptor mRNA expression. This was done using 33P-labelled oligonucleotide-specific probes for rat H3 receptor mRNA. Unlike rat brain, where H3 receptor mRNA expression was found to be abundant in several regions, no H3 receptor mRNA expression could be detected in the rat ileum under the conditions used. These findings suggest H3 receptors have no role in the modulation of cholinergic neuronal function in the rat or human intestine unlike those in the guinea-pig. Furthermore, H3 receptors appear to be absent in the rat ileum.
Insights
Histamine H3 receptors do not modulate cholinergic nerve function in rat or human intestines. Studies found no H3 receptor mRNA expression in the rat ileum, suggesting their absence.
Area of Science:
- Pharmacology
- Neurogastroenterology
- Molecular Biology
Background:
- Histamine H3 receptors are known to modulate neurotransmission in various tissues.
- Their role in the mammalian enteric nervous system, particularly in the rat ileum and human colon, remains less understood.
- Previous studies suggest a role in guinea-pig intestine.
Purpose of the Study:
- To investigate the effects of histamine and a selective H3 receptor agonist on cholinergic nerve-mediated contractions in the rat ileum and human colon.
- To determine the presence of H3 receptor mRNA in the rat ileum using in situ hybridisation histochemistry (ISHH).
Main Methods:
- Electrically stimulated contractile responses of rat ileum (longitudinal and circular muscles) and human colon (circular muscle) were measured.
- The effects of histamine and (R)alpha-methylhistamine were assessed on these contractions.
- In situ hybridisation histochemistry (ISHH) with 33P-labelled probes was used to detect H3 receptor mRNA in rat brain and ileum.
Main Results:
- Neither histamine nor (R)alpha-methylhistamine significantly affected cholinergic nerve-stimulated contractions in the rat ileum or human colon.
- Contractions induced by substance P and nicotine were also unaffected by histamine or (R)alpha-methylhistamine.
- H3 receptor mRNA was abundant in rat brain but not detectable in the rat ileum under the experimental conditions.
Conclusions:
- Histamine H3 receptors do not appear to play a role in modulating cholinergic neuronal function in the rat or human intestine.
- H3 receptors seem to be absent in the rat ileum.
- These findings contrast with observations in guinea-pig intestine, highlighting species-specific differences in H3 receptor function.