Identification of histamine receptors and effects of histamine on murine and simian colonic excitability.

Background: Inflammatory responses can include recruitment of cells of hematopoietic origin to the tunica muscularis. These cells can secrete a variety of factors which can reset the gain of smooth muscle cells (SMC) and influence motor patterns. Histamine (H), a major mediator in inflammation, is released by mast cells and exerts diverse effects in SMC by binding to H receptors. The profiles of H receptor expression in animal models used to study inflammatory diseases are unknown.

Methods: Histamine receptor expression and electro-mechanical responses to H were tested in simian and murine colonic smooth muscle using qualitative and quantitative PCR, isometric force measurements, microelectrode recordings and patch clamp techniques.

Key Results: H1, H2, and H4 receptor transcripts were expressed at similar levels in simian colonic tissue whereas only the H2 receptor transcript was detected in murine colonic tissue. Stimulation of simian colonic muscles with H caused depolarization and contraction in the presence of tetrodotoxin. Histamine activated non-selective cation channels in simian SMC. In contrast, H caused hyperpolarization and inhibited contractions of murine colon. The hyperpolarization was inhibited by the K(ATP) channel blocker, glibenclamide. Histamine-activated K(+) currents were inhibited by glibenclamide in murine colonic SMC.

Conclusions & Inferences: Histamine receptor expression in simian SMC was similar to that reported in humans. However, H receptor profile and responses to H were considerably different in mice. Thus, monkey colon may be a more suitable model to study how inflammatory mediators affect the gain of smooth muscle excitability.