Role of Corticotrophin-releasing Factor in the Stress-induced Dilation of Esophageal Intercellular Spaces

Corticotrophin-releasing factor (CRF) plays a major role in coordinating stress responses. We aimed to test whether blocking endogenous CRF activity can prevent the stress-induced dilation of intercellular spaces in esophageal mucosa. Eighteen adult male rats were divided into 3 groups: 1) a non-stressed group (the non-stressed group), 2) a saline-pretreated stressed group (the stressed group), 3) and an astressin-pretreated stressed group (the astressin group). Immediately after completing the experiments according to the protocol, distal esophageal segments were obtained. Intercellular space diameters of esophageal mucosa were measured by transmission electron microscopy. Blood was sampled for the measurement of plasma cortisol levels. Mucosal intercellular spaces were significantly greater in the stressed group than in the non-stressed group. Mucosal intercellular spaces of the astressin group were significantly smaller than those of the stressed group. Plasma cortisol levels in the stressed group were significantly higher than in the non-stressed group. Pretreatment with astressin tended to decrease plasma cortisol levels. Acute stress in rats enlarges esophageal intercellular spaces, and this stress-induced alteration appears to be mediated by CRF. Our results suggest that CRF may play a role in the pathophysiology of reflux-induced symptoms or mucosal damage.

Variation of the intercellular space in the esophageal epithelium in response to hydrochloridric acid infusion in patients with erosive esophagitis

The purpose of this study was to compare esophageal infusion with 0.1 N hydrochloridric acid (HCl) to esophageal infusion with saline in patients presenting with typical gastroesophageal reflux symptoms and erosive esophagitis. METHODS: Upper gastrointestinal endoscopy was performed on 44 prospective subjects, 29 of whom were included in the study. Eighteen patients presented with normal esophagi (Control Group "C"), nine of whom were infused with HCl and nine with saline. Eleven patients presented with erosive esophagitis (Lesion Group "L"), five of whom were infused with HCl and six with saline. Biopsies of the esophageal mucosa were collected before and after infusions. RESULTS: No statistically significant difference was found between the two types of infusions in terms of the dilation of the intercellular space of the esophageal epithelium, regardless of the status of the patient. CONCLUSIONS: Response to HCl infusion cannot be used as a marker for gastroesophageal reflux disease.

Cross talk between P2 purinergic receptors modulates extracellular ATP-mediated interleukin-10 production in rat microglial cells

Previously we demonstrated that ATP released from LPS-activated microglia induced IL-10 expression in a process involving P2 receptors, in an autocrine fashion. Therefore, in the present study we sought to determine which subtype of P2 receptor was responsible for the modulation of IL-10 expression in ATP-stimulated microglia. We found that the patterns of IL-10 production were dose-dependent (1, 10, 100, 1,000 micrometer) and bell-shaped. The concentrations of ATP, ATP-gammaS, ADP, and ADP-beta S that showed maximal IL-10 release were 100, 10, 100, and 100 micrometer respectively. The rank order of agonist potency for IL-10 production was 2'-3'-O-(4-benzoyl)-benzoyl ATP (BzATP) = dATP > 2-methylthio-ADP (2-meSADP). On the other hand, 2-methylthio-ATP (2-meSATP), alpha,beta-methylene ATP (alpha,beta-meATP), UTP, and UDP did not induce the release of IL-10 from microglia. Further, we obtained evidence of crosstalk between P2 receptors, in a situation where intracellular Ca2+ release and/or cAMP-activated PKA were the main contributors to extracellular ATP-(or ADP)-mediated IL-10 expression, and IL-10 production was down- regulated by either MRS2179 (a P2Y1 antagonist) or 5'-AMPS (a P2Y11 antagonist), indicating that both the P2Y1 and P2Y11 receptors are major receptors involved in IL-10 expression. In addition, we found that inhibition of IL-10 production by high concentrations of ATP-gammaS (100 micrometer) was restored by TNP-ATP (an antagonist of the P2X1, P2X3, and P2X4 receptors), and that IL-10 production by 2-meSADP was restored by 2meSAMP (a P2Y12 receptor antagonist) or pertusis toxin (PTX; a Gi protein inhibitor), indicating that the P2X1, P2X3, P2X4 receptor group, or the P2Y12 receptor, negatively modulate the P2Y11 receptor or the P2Y1 receptor, respectively.

Propranolol stimulates testicular interstitial fluid formation and testosterone secretion in rats

We investigated the effect of intratesticularly injected propranolol on testicular interstitial fluid (TIF) formation and on testosterone levels in the TIF of intact adult male Wistar rats (4-9 rats per group). D1-propranolol at doses of 0.6, 1.2 or 6.0 mg/kg was injected into the left (L) testis whereas the right (R) testis (control testis) received vehicle. d1-propranolol (6.0 mg/kg) caused a significant increase in both TIF volume (329 per cent) and TIF levels of testosterone (257 per cent) in the L testis but not in the R (control) testis 3 h post-injection. In rats treated simultaneously with human chorionic gonadotropin (hCG, 5 IU/rat, sc) the same dose of propranolol (6.0 mg/kg) significantly increased the stimulatory effect of hCG on testosterone secretion by 1.8-fold, but hCG did not modify the stimulatory effect of propranolol on TIF volume. These results demonstrate a direct stimulatory effect of propranolol on TIF volume and testosterone secretion, both under basal and hCG-stimulated conditions.