Functional interaction between transforming growth factor alpha and capsaicin-sensitive sensory neurons in the rat stomach.

BACKGROUND AND AIMS: Transforming growth alpha (TGFalpha) and sensory neurons have been shown to promote gastric mucosal protection and healing. Aims were to examine in vitro interactions between gastric sensory neurons, the sensory neuropeptide calcitonin gene-related peptide (CGRP), and TGFalpha. METHODS: Gastric mucosal/submucosal tissue fragments from Sprague-Dawley (SD) rats were incubated in short-term (30 min) culture. Peptide release into media and TGFalpha tissue content were measured by radioimmunoassay. RESULTS: TGFalpha (1 x 10(-8) to 1 x 10(-6) M) caused dose-dependent stimulation of CGRP release. Maximal CGRP release (+87%) was observed with 1 x 10(-6) M TGFalpha: 28.6+/-3.8 vs. control of 15.5+/-2.7 pg/g tissue; P<0.05. Both CGRP (1 x 10(-7) to 1 x 10(-5) M) and capsaicin (1 x 10-(8) to 1 x 10(-6)M) significantly inhibited basal TGFalpha release in a dose-dependent fashion that ranged from -20% to -39%. In contrast, capsaicin-induced sensory denervation caused significant increases in both basal TGFalpha release and TGFalpha tissue content. CONCLUSION: Function interactions between TGFalpha and gastric sensory neurons are suggested by the observations that (1) TGFalpha stimulated CGRP release from gastric sensory neurons; (2) CGRP and acute capsaicin treatment inhibited TGFalpha release and; (3) capsaicin-induced sensory denervation caused significant increases in both gastric TGFalpha basal release and tissue content.

Mechanisms of transforming growth factor-alpha (TGF-alpha) induced gastroprotection against ethanol in the rat: roles of sensory neurons, sensory neuropeptides, and prostaglandins.

The mechanisms by which transforming growth factor-a (TGP-alpha) protects the stomach against mucosal injury are incompletely understood. The aim of this study was to examine the roles of sensory neurons, sensory neuropeptides and prostaglandins in TGFalpha gastroprotection against ethanol. Fasted rats received TGF-alpha (50 microg/kg, intraperitoneally) prior to orogastric ethanol (75% v/v, 1 ml). Gastric injury was quantitated 30 min after ethanol. Involvement of sensory neurons and the sensory neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), were examined by capsaicin deafferentation and specific receptor antagonist infusion, respectively. Indomethacin (10 mg, intragastrically) was used to determine the role of prostaglandins in TGF-alpha-mediated gastroprotection. TGF-alpha significantly diminished ethanol-induced gastric lesion area to 5.7 +/- 0.8 mm2 vs 41.1 +/- 5.2 mm2 (p < 0.001). Sensory denervation and CGRP-receptor blockade abolished the TGF-alpha protective effect. In contrast, SP antagonist and indomethacin did not alter TGF-alpha gastroprotection. In conclusion, TGF-alpha-mediated gastroprotection involves sensory neuron activation and CGRP release and this protective effect did not involve substance P or prostaglandin generation.

Transforming growth factor alpha-mediated gastroprotection against stress ulceration in the rat: involvement of capsaicin-sensitive sensory neurons.

Exogenously administered TGF alpha has been shown to protect rodent gastric mucosa against injury caused by acid-dependent and acid-independent injury. The present study examined whether the gastroprotective effects of TGF alpha on stress-induced gastric ulceration in the rat involves activation of capsaicin-sensitive sensory neurons. Fasted male SD rats were subjected to water restraint stress (WRS) for four hours. Thereafter, rats were euthanized; the stomach opened and macroscopic areas of gastric ulceration quantitated (mm(2)). Gastric tissue contents of TGF alpha and the sensory neuropeptide, calcitonin gene-related peptide (CGRP) were determined by radioimmunoassay. Prior to stress rats received TGF alpha 50, 100 or 200 microg/kg by intraperitoneal injection. Sensory denervation was accomplished by high dose capsaicin treatment. WRS caused severe ulceration in the gastric corpus; 46.1 + 6.6 mm(2). Parenteral administration of TGF alpha caused dose-dependent reduction in gastric injury: 34.7 + 4.9 mm(2) with 50 microg/kg (p < 0.05); 25.4 + 3.6 mm(2) with 100 microg/kg (p < 0.001) and 9.4 + 0.8 mm(2) with 200 microg/kg (p < 0.001). The gastroprotective action of TGF alpha (200 microg/kg, i.p.) was abolished by capsaicin-induced sensory denervation. In addition, WRS ulceration was associated with significant reduction in gastric CGRP (-42%) and TGF alpha (-48%) content. Reduction in CGRP content was prevented by TGF alpha pretreatment. We conclude that: 1) TGF alpha caused dose-dependent gastroprotection against WRS ulceration, 2) TGF alpha-mediated gastric mucosal protection was prevented by capsaicin-induced sensory denervation and, 3) stress-induced injury was associated with significant reduction in gastric content of both TGF alpha and CGRP.

Primary aortoenteric fistula to jejunum: a case report.

Primary aortoenteric fistula (PAEF) is a well-known but rare cause of gastrointestinal bleeding. The diagnosis can be difficult since the majority of patients do not have classical symptoms. "Herald bleed" is usually followed by a massive hemorrhage. Endoscopy and radiographic studies can assist in diagnosis. We present the case of 56-year-old male with PAEF who presented with obscure gastrointestinal bleeding. Endoscopic studies were unremarkable. Computed tomography (CT) in this stable but symptomatic patient helped in establishing diagnosis of PAEF. Patient underwent laparotomy with aortobifemoral graft placement. A high index of suspicion, early diagnosis and prompt appropriate surgical intervention are crucial for survival of these patients.