Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Specific polyclonal antibodies raised against synthetic thyrotropin-releasing hormone (TRH) infused intracerebroventricularly (ICV) significantly decreased gastric lesions induced by cold restraint stress. The antiulcer effect of immunologic blockade of brain TRH was specific. Normal rabbit serum or antibodies raised against somatostatin, alpha-MSH, Leu-enkephalin, gonadotropin-releasing hormone and atrial natriuretic factor were ineffective. These findings suggest that brain TRH may play an important role in experimental stress ulcer formation.
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PMID:Evidence for a role of brain thyrotropin-releasing hormone (TRH) on stress gastric lesion formation in rats. 211 18

Bilateral microinjections of the opiate antagonist naloxone (0.1, 1.0 and 10.0 micrograms) into the central nucleus of the amygdala (CEA) produced a significant potentiation of cold restraint-induced gastric pathology in rats. The opiate agonist, beta-endorphin (0.1, 1.0 and 10.0 micrograms), on the other hand, inhibited stress ulcer formation in a dose-related manner. Stress ulcer-attenuating effects were also seen with intra-CEA injections of the enkephalin analogs [D-Ala2,D-Leu5]enkephalin (10.0 micrograms) and [D-Ala2]Met-enkephalinamide (10.0 micrograms). Pretreatment of rats with naloxone (1.0 microgram) completely antagonized and even reversed the gastric cytoprotective effects of beta-endorphin (1.0 and 10.0 micrograms). The results indicate that the CEA is important in the gastric cytomodulatory effects of endogenous opiates during stressful experiences.
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PMID:Opiate mechanisms in the central amygdala and gastric stress pathology in rats. 283 14

When rats were exposed to immobilization stress for 1-12 h, gastric lesions did not occur at 1-6 h but did at 12 h of immobilization. Exogenous adenosine increased stress-induced gastric lesions, and dipyridamole, a blocker of adenosine uptake, potentiated the action of adenosine. The selective adenosine A1-receptor stimulants N6-cyclohexyl adenosine (CHA) and N6-(L-phenylisopropyl) adenosine (L-PIA) produced gastric lesions even in non-stressed state and markedly potentiated in dose- and time-dependent manner in stressed state. The stimulatory effect of N6-(D-phenylisopropyl) adenosine (D-PIA) on ulceration was weaker than that of CHA or L-PIA. Furthermore, intracerebral ventricular (i.c.v.) injection of adenosine or adenosine analogues produced the most rapid and most potent exacerbation of stress-induced gastric lesions relative to those induced with subcutaneous (s.c.) injection. The stress lesions enhanced by CHA were not affected by phentolamine, yohimbine, prazosin, naloxone and cholecystokinin (CCK8) but were inhibited by caffeine, clonidine, morphine and beta-endorphin. The inhibitory effect of clonidine was not antagonized by yohimbine or prazosin. The inhibition by morphine was selectively antagonized by exogenous CCK8 as well as naloxone. These results suggest that endogenous adenosine is tonically active in stress lesion formation which is modulated by opiate systems. Clonidine as well as caffeine may function as a purinoceptor antagonist, and it seems unlikely that the inhibitory effect of clonidine on stress ulcer is due to activation of alpha-adrenoceptors.
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PMID:Development of stress-induced gastric lesions involves central adenosine A1-receptor stimulation. 299 4

Strain differences in stress responsiveness have been previously described, but specific components of the hypothalamic-pituitary-adrenal (HPA) axis responsible for stress hypo- or hyperactivity have not yet been characterized. This study proposed to analyze the effect of restraint stress on different measures of HPA function and stress ulcer in stress-ulcer prone Wistar-Kyoto (WKY) and Fisher 344 (F-344) rats and in the ulcer-resistant Wistar strain. Adult male rats of these strains were sham adrenalectomized, adrenalectomized, and adrenalectomized-replaced with corticosterone pellet. Ten days after surgery, animals were subjected to the 2-h ulcerogenic water-restraint stress and killed 2 h later. Intact WKY rats had dramatically more ulcers and higher anterior pituitary adrenocorticotropic hormone (ACTH) and proopiomelanocortin mRNA levels than the other two strains. In WKY rats, adrenalectomy increased ulcer incidence but did not affect thymus weight, ACTH content, or hypothalamic corticotropin-releasing factor mRNA levels, in contrast to the profound effects of adrenalectomy on these parameters in the other strains. Furthermore, corticosterone replacement was either without effect or enhanced the effect of adrenalectomy on these parameters in WKY rats, while it reversed the effects of adrenalectomy in the other strains. These data imply that WKY rats respond to stress with enhanced and prolonged changes in peripheral functions that are regulated by glucocorticoids, suggesting the presence of impaired efficacy of the glucocorticoid negative feedback on HPA function.
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PMID:Strain differences in hypothalamic-pituitary-adrenal activity and stress ulcer. 814 89

Cimetidine is commonly used for stress ulcer prophylaxis in intensive care patients. Cimetidine contains an imidazole structure. Similar drugs have been shown to inhibit steroid synthesis by blocking cytochrome P450-dependent reactions in the adrenal cortex. It is suggested that bolus injections of cimetidine suppress the normal corticosteroid production. This might be deleterious since a decreased cortisol response seems to be associated with increased mortality during chronic severe stress. We therefore performed a prospective, randomized, and controlled study to assess the effect of a short-term continuous infusion of either cimetidine or ranitidine, a non-imidazole H2-pantagonist, upon cortisol secretion in a cohort of hemodynamically stable intensive care patients. Twenty patients were consecutively enrolled following determined inclusion criteria and divided in three treatment groups: 6 controls, 7 cimetidine- and 7 ranitidinetreated subjects. Both cimetidine (1200 mg) and ranitidine (200 mg) were administered by infusion pump over 24 hrs. A short corticotropin test was done within 24 hrs after admission (d0) and repeated 7 days thereafter (d7). On both occasions, plasma cortisol was measured immediately before the test and 30 min afterwards. The three treatment groups presented a normal cortisol response at d0 and d7. Peak cortisol levels after stimulation did not show any significant difference for both the cimetidine and the ranitidine group, either at d0 or at d7. Moreover, this response at d0 and d7 was also not significantly different from the one observed in the controls. From this study we can conclude that one week treatment with conventional intravenous doses of cimetidine does not induce significant alterations of the cortisol response in hemodynamically stable ICU patients.
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PMID:One week treatment with cimetidine does not attenuate the cortisol response to a short corticotropin test in stable intensive care patients: a prospective, randomized, and controlled study. 866 19

When exposed to prolonged stress, rats develop gastric ulceration, enhanced colon motility with depletion of its mucin content and signs of physiological and behavioral arousal. In this model, we tested whether antidepressants (fluoxetine and bupropion), anxiolytics (diazepam and buspirone) or the novel nonpeptide corticotropin-releasing hormone (CRH) type-1 receptor (CRH-R1) antagonist, antalarmin, modify these responses. Fluoxetine, bupropion, diazepam and antalarmin all suppressed stress-induced gastric ulceration in male Sprague-Dawley rats exposed to four hours of plain immobilization. Antalarmin produced the most pronounced anti-ulcer effect and additionally suppressed the stress-induced colonic hypermotility, mucin depletion, autonomic hyperarousal and struggling behavior. Intraperitoneal CRH administration reproduced the intestinal but not the gastric responses to stress while vagotomy antagonized the stress-induced gastric ulceration but not the intestinal responses. We conclude that brain CRH-R1 and vagal pathways are essential for gastric ulceration to occur in response to stress and that peripheral CRH-R1 mediates colonic hypermotility and mucin depletion in this model. Nonpeptide CRH-R1 antagonists may therefore be prophylactic against stress ulcer in the critically ill and therapeutic for other pathogenetically related gastrointestinal disorders such as peptic ulcer disease and irritable bowel syndrome.
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PMID:Marked suppression of gastric ulcerogenesis and intestinal responses to stress by a novel class of drugs. 1208 65