INCREASED SUSCEPTIBILITY OF GASTRIC-MUCOSA TO ULCEROGENIC STIMULATIONIN DIABETIC RATS - ROLE OF CAPSAICIN-SENSITIVE SENSORY NEURONS

1. We examined the gastric mucosal blood flow (GMBF) and ulcerogenic r esponses following barrier disruption induced by sodium taurocholate ( TC) in diabetic rats and investigated the role of capsaicin-sensitive sensory neurons in these responses. 2 Animals were injected streptozot ocin (STZ: 70 mg kg(-1), i.p.) and used after 5, 10 and 15 weeks of di abetes with blood glucose levels of >350 mg dl(-1). The stomach was mo unted on an ex-vivo chamber under urethane anaesthesia and exposed to 20 mM TC plus 50 mM HCl for 30 min in the presence of omeprazole. Gast ric transmucosal potential difference (PD), GMBF, and luminal acid los s (HL back-diffusion) were measured before and after exposure to 20 mM TC, and the mucosa was examined for lesions 90 min after TC treatment . 3 Mucosal application of TC caused PD reduction in all groups; the d egree of PD reduction was similar between normal and diabetic rats, al though basal PD values were lower in diabetic rats. In normal rats, TC treatment caused luminal acid loss, followed by an increase of GMBF, resulting in minimal damage in the mucosa. 4 The increased GMBF respon ses associated with H+ back-diffusion were mitigated in STZ-treated ra ts, depending on the duration of diabetes, and severe haemorrhagic les ions occurred in the stomach after 10 weeks of diabetes. 5 Intragastri c application of capsaicin increased GMBF in normal rats, but Such res ponses were mitigated in STZ diabetic rats. The amount of CGRP release d in the isolated stomach in response to capsaicin was significantly l ower in diabetic rats when compared to controls. 6 The deleterious inf luences on GMBF and mucosal ulcerogenic responses in STZ-diabetic rats were partially but significantly antagonized by daily insulin (4 unit s rat(-1)) treatment. 7 These results suggest that the gastric mucosa of diabetic rats is more vulnerable to acid injury following barrier d isruption, and this change is insulin-sensitive and may be partly acco unted for by the impairment of GMBF response associated with acid back -diffusion and mediated by capsaicin-sensitive sensory neurons.