Lack of evidence for histamine H3 receptor function in rat ileum and human colon

The effects of histamine and the more selective H3 receptor agonist (R)α-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 µM) and (R)α-methylhistamine (0.1–3.0 µM) 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 µM) and nicotine (0.1 µM), which both produce a contraction via activation of cholinergic nerves, were also unaffected by histamine (1 µM and 10 µM) or (R)α-methylhistamine (1 µM and 10 µM), 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.