Capsaicin-Sensitive Sensory Nerves in Recovery of Gastric Mucosal Integrity after Damage by Sodium Taurocholate in Rats

Abstract

ABSTRACT-We compared the recovery process of gastric mucosal integrity after damage by 20 mM sodium taurocholate (TC) in control, sensory deafferented and indomethacin-treated rats. Under anesthe tized conditions, the stomach was mounted on a chamber and perfused with saline or 50 mM HCI. Applica tion of TC (30 min) to the saline-perfused stomach produced a marked reduction in the potential difference (PD) (surface epithelial damage), followed by increases of gastric mucosal blood flow (GMBF) and luminal pH (alkalinization), but there was a rapid recovery of PD without development of gross lesions. Chemical ablation of capsaicin-sensitive sensory nerves had no influence on the PD reduction and luminal alkaliniza tion, but significantly inhibited the rise in GMBF and the PD recovery. Indomethacin pretreatment (5 mg/kg, s.c.) significantly inhibited these changes seen after exposure to TC, except for PD reduction. In con trast, TC caused a sizable amount of H+ back-diffusion and a more pronounced and persistent rise in GMBF in the stomach perfused with 50 mM HCI, yet only minimal damage was observed in the control animals. Under these conditions, both sensory deafferentation and indomethacin inhibited such GMBF responses, leading to hemorrhagic damage without affecting the degree of H+ back-diffusion. These results suggest that capsaicin-sensitive sensory nerves contribute to the recovery of gastric mucosal integrity after damage, probably by maintaining GMBF responses associated with H+ back-diffusion and preventing the later extension to gross damage in the presence of acid.

Facilitation by Endogenous Prostaglandins of Capsaicin-Induced Gastric Protection in Rodents through EP2 and IP Receptors

“…Although gastric hyperemia is not the exclusive mechanism of gastric cytoprotection as induced by PGE 2 or capsaicin-sensitive afferent neurons (Stroff et al, 1996;Araki et al, 2000), GMBF is considered to be a factor in capsaicin-induced gastric protection under certain experimental conditions (Holzer et al, 1991;Takeuchi et al, 1993). We previously reported that the gastric hyperemic response to capsaicin was also significantly mitigated by indomethacin, suggesting an involvement of endogenous PGs in this action (Matsumoto et al, 1992).…”

“…Several studies, including our own, have shown that the protective effect of capsaicin is mitigated by prior administration of indomethacin, suggesting an involvement of endogenous PGs in this action (Takeuchi et al, 1991b(Takeuchi et al, , 1993Uchida et al, 1991;Brzozowski et al, 1993). It is known that endogenous PGs sensitize the sensory neurons to nociceptive stimulation (Ohishi et al, 1999;Ueno et al, 2000).…”

Cyclooxygenase Isozymes Involved in Adaptive Functional Responses in Rat Stomach after Barrier Disruption

“…It is known that the stomach responds to mucosal-damaging agents by altering various functions such as mucosal blood flow (Nobuhara and Takeuchi, 1984;Takeuchi et al, 1986Takeuchi et al, , 1993. Although the role of PGs may vary with different types of mucosal irritants used to break the gastric mucosal barrier in the presence of luminal acid, this process is essentially mediated by endogenous PGs when the barrier is disrupted by TC (Nobuhara and Takeuchi, 1984;Takeuchi et al, 1986;Hirata et al, 1997).…”

“…It is known that the application of mild irritants to the stomach causes an increase in gastric mucosal blood flow (GMBF) as well as a decrease in acid secretion (Whittle, 1983;Takeuchi et al, 1986Takeuchi et al, , 1993. These agents damage the surface epithelium of the gastric mucosa, resulting in acid back-diffusion, yet they rarely cause macroscopically visible damage and actually protect the stomach against necrotizing agents (Holzer et al, 1991;Takeuchi et al, 1993).…”

“…These agents damage the surface epithelium of the gastric mucosa, resulting in acid back-diffusion, yet they rarely cause macroscopically visible damage and actually protect the stomach against necrotizing agents (Holzer et al, 1991;Takeuchi et al, 1993). Such hyperemic responses subside in the presence of NSAIDs, suggesting a role for endogenous PGs in this phenomenon (Whittle, 1983;Nobuhara and Takeuchi, 1984;Takeuchi et al, 1986Takeuchi et al, , 1987.…”