Role of non-adrenergic non-cholinergic inhibitory nerves in the colon of patients with ulcerative colitis

Abstract

The cause of impaired colonic motility in patients with ulcerative colitis (UC) is unknown. The non-adrenergic non-cholinergic (NANC) inhibitory nervous system is one of the most important factors in the enteric nervous system of human gut. To assess the physiological significance of NANC inhibitory nerves in the colon of patients with UC, we investigated the enteric nerve responses of colonic tissues from patients with this disease. Colonic tissues were obtained from the lesional sigmoid colons of six patients with UC. Normal sigmoid colonic tissues obtained from ten patients with colonic cancer were used as controls. A mechanographic technique was used to evaluate in-vitro muscle responses to the electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. NANC inhibitory nerves were found to act on both normal colon and the lesional colon of patients with UC, but colon with UC was more strongly innervated by NANC inhibitory nerves than was the normal colon. These findings suggest that NANC inhibitory nerves play an important role in the impaired motility observed in the colon of patients with UC.

Tachykinin NK2Receptor and Functional Mechanisms in Human Colon: Changes with Indomethacin and in Diverticular Disease and Ulcerative Colitis

“…The enhanced TTX-resistant contractions were reduced by SR140333, suggesting that, in DD, there is unmasking of the actions of TTX-resistant terminals that release tachykinin(s); alterations in cannabinoid mechanisms were also reported (Guagnini et al, 2006) ]NKA(4 -10) was also seen in UC, although the effect was not as great as that seen in DD. This decreased contractility to NKA and SP has been reported previously (Tomita et al, 2000;Menzies et al, 2001;Liu et al, 2002), and mechanisms have been explored. For example, in UC, there is evidence that interleukin-6 (Vrees et al, 2002) and hydrogen peroxide (Cao et al, 2004) contribute to the decrease of NKAinduced Ca 2ϩ release from intracellular Ca 2ϩ stores.…”

NK2 Receptor-Mediated Spontaneous Phasic Contractions in Normal and Ulcerative Colitis Human Sigmoid Colon

“…Abnormal colonic motor function occurs in patients with ulcerative colitis (Koch et al, 1988;Tomita et al, 1998;Al-Saffar and Hellstrom, 2001) and in animal models of colitis (Sethi and Sarna, 1991;Lu et al, 1997;Tsukamoto et al, 1997;Hosseini et al, 1999;Shi and Sarna, 2000;Gonzalez and Sarna, 2001). We have shown that neurokinin A and EFS-induced contraction were reduced in ulcerative colitis.…”

Generalized loss of inhibitory innervation reverses serotonergic inhibition into excitation in a rabbit model of TNBS‐colitis

“…It should be mentioned that all these observations are at variance with other functional and immunohistochemical studies. Indeed Tomita et al (1998) reported that the colon from patients with UC was more strongly innervated by NANC inhibitory nerves, with NO as major neurotransmitter, than was the normal colon and Belai et al (1997) observed increased VIP, NOS and PACAP immunoreactivity in the myenteric plexus and nerve ®bres of the circular muscle layer of the a icted segment of the ileum of patients with Crohn's disease. The reason for this discrepancy is unclear but it would be of interest to study the role of VIP-ergic neurotransmission in our model.…”