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

The effects of histamine and the more selective H-3 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 muM) and (R)alpha -methylhistamine (0.1-3.0 muM) 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 muM) and nicotine (0.1 muM), which both produce a contraction via activation of cholinergic nerves, were also unaffected by histamine (1 muM and 10 muM) or (R)alpha -methylhistamine (1 muM and 10 muM), in either tissue. Preliminary studies using in situ hybridisation histochemistry (ISHH) were performed in rat brain and ileum in an attempt to identify H-3 receptor mRNA expression. This was done using P-33-labelled oligonucleotide-specific probes for rat H-3 receptor mRNA. Unlike rat brain, where Hg receptor mRNA expression was found to be abundant in several regions, no H-3 receptor mRNA expression could be detected in the rat ileum under the conditions used. These findings suggest H-3 receptors have no role in the modulation of cholinergic neuronal function in the rat or human intestine unlike those in the guinea-pig. Furthermore, H-3 receptors appear to be absent in the rat ileum.