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

Abstract

Abstract. Nicotine has been shown to reduce both tone and muscular activity in the human colon by releasing nitric oxide (NO) from nerves. To our knowledge, however, the effect of nicotine on mouse colon has not been elucidated, and the response in tissue from ulcerative colitis (UC) has not been investigated. We examined nicotine-induced responses in colon from control mice and mice with dextran sodium sulfate (DSS)-induced UC. In controls, bath application of nicotine caused a transient relaxation in longitudinal preparations from the transverse and distal colons but not from the rectum. The response was observed in the presence of bethanechol, abolished by treatment with tetrodotoxin and hexamethonium, and mediated partially (>50%) by the NO pathway. In longitudinal preparations of the distal colon from DSStreated mice, spontaneous contractions decreased markedly, and nicotine caused contraction without relaxation in half of the preparations tested. Nicotine-induced relaxation in the presence of bethanechol was significantly decreased in the DSS-treated distal colon without changing bethanechol-induced contractions. These data suggest that 1) responses to nicotine differ dependent on colon regions, 2) DSS treatment predominantly caused nicotine-sensitive neurogenic changes in distal colon, and 3) DSS treatment may reverse the direction of nicotine-evoked responses in the colon, in mice.

Thromboxane-prostanoid receptor expression and antagonism in dextran-sodium sulfate-induced colitis

“…Borjesson and Delbro [25] found significantly increased muscle tone and a tendency toward increased contraction in the rat distal colon with DSS; however, Gonzalez and Sarna [26], also studying DSS in rats, found no change in spontaneous colonic contractions. Moreover, Murakami et al [27] found decreased spontaneous contractions in the DSS mouse colon, in contrast to our finding of an approximate twofold more rapid propulsion through the distal colon (though not statistically significant; Fig. 4b).…”

Nicotinic Regulation of Energy Homeostasis

“…However, some basic insights have been obtained. In most species and experimental preparations, nicotine causes contraction of stomach, jejunal, and ileal muscles, and relaxation of colonic muscles and lower oesophageal sphincter (Braverman et al, 2011;Murakami et al, 2009;Vural, Ozturk Fincan, Bozkurt, Ercan, & Sarioglu, 2009). At a more integrated level, nAChRs are thought to play a crucial role in ascending reflexes but only a minor role in descending reflexes of the myenteric plexus, whereas in the submucosal plexus, most nAChRs are associated with descending projections (Galligan & North, 2004).…”

Interleukin-19 Is a Negative Regulator of Innate Immunity and Critical for Colonic Protection

“…These findings provided two new insights into the pathogenesis of IBD at that time: the first one is that a genetic factor lead to mucosal inflammation that resembles IBD and the second one is that altered immune responses contribute to the initiation and chronification of IBD. The most widely used IBD animal models are colitis chemically induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) (10), oxazolone (11), and dextran sodium sulfate (DSS) (12,13) (Table 1). Importantly, transfer of a T cell population (CD4 + CD45RB high T cells) that lacks regulatory T cells into scid or Rag −/− animals induced colonic inflammation (14) ( Table 1).…”