Lack of evidence for histamine H 3 receptor function in rat ileum and human colon

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.

Nicotine-Induced Neurogenic Relaxation in the Mouse Colon: Changes With Dextran Sodium Sulfate–Induced Colitis

“…A report described contractions induced by nicotine in circular muscle preparations from the human (probably sigmoid or distal) colon via the release of ACh (7). Although it has been established that treatment with nicotine causes contractions in the ileum in various species including mice (7,8,15), a recent report showed that nicotine induced relaxation of the mouse ileum in the presence of atropine (16). Interestingly, we found that DSS treatment caused a change from relaxation to contraction of nicotine-induced contractile responses in longitudinal preparations of the distal colon in half of the treated mice.…”

“…In isolated proximal and distal colons from rats (9), proximal colon from dogs (10), and opossum ileocolonic junction (11), treatment with nicotine caused neurogenic relaxation. Relaxation induced by nicotine has also been reported in the human colon (4, 12 -14), although nicotine caused contractions with the release of ACh in circular preparations from human colon (7). Nicotine-induced contractions have been established in the jejunum and ileum in mice (15 -17), although Okishio et al (16) reported that nicotine induced relaxation of circular muscle of the mouse ileum in the presence of atropine.…”

“…For instance, treatment with nicotine produced a contraction of the longitudinal muscle of the ileum that was mediated by the release of acetylcholine (ACh) in rats (7) and guinea pig (8). In isolated proximal and distal colons from rats (9), proximal colon from dogs (10), and opossum ileocolonic junction (11), treatment with nicotine caused neurogenic relaxation.…”

Histamine Receptor Expression in the Gastrointestinal Tract of Dogs

“…Interestingly, the H3R agonist (R)a-methylhistamine has been shown to inhibit nerve-mediated contractions in the guinea pig ileum (Izzo et al, 1998). However, several studies have demonstrated H3R to be only scantly expressed or absent from the gastrointestinal tract, including the enteric nervous system, of humans and rats (Hemedah et al, 2001;Sander et al, 2006;Boer et al, 2008). In addition, no functional effect of the H3R agonist (R)a-methylhistamine has been shown on cholinergic nerve stimulation of muscular layers in the rat ileum and the human colon (Hemedah et al, 2001).…”

“…However, several studies have demonstrated H3R to be only scantly expressed or absent from the gastrointestinal tract, including the enteric nervous system, of humans and rats (Hemedah et al, 2001;Sander et al, 2006;Boer et al, 2008). In addition, no functional effect of the H3R agonist (R)a-methylhistamine has been shown on cholinergic nerve stimulation of muscular layers in the rat ileum and the human colon (Hemedah et al, 2001). Moreover, H3R has been demonstrated to be functionally absent from the canine colon, and this suggests H3R to be of minor importance for gastrointestinal function in many animals species including dogs (Rangachari and Prior, 1994).…”