The effect of nicotine on ethanol-induced gastric ulcers in rats

Summary Nicotine, in concentrations of 5 and 25 g/ml drinking water, given ad libitum for 10 days, dose-dependently increased lesion formation and worsened ethanol-induced ulceration in rat stomachs. Daily fluid intake and b.wt gain were not adversely affected by nicotine pretreatment.The authors are grateful to Mr C.T. Luk for his skilled technical assistance.     

The influence of chronic nicotine treatment on stress-induced gastric ulceration and emptying rate in rats

Ten-day treatment with nicotine, (5, 25 or 50 g/ml drinking water) dose-dependently intensified gastric ulceration induced by cold-restraint, and emptying rate. Stomach contractions produced by graded doses of bethanechol i.v. were elevated further by nicotine treatment. It is suggested that chronic nicotine administration produces hypersensitivity of the gastric muscarinic receptors; stomach hypermotility contributes to the ulcer-worsening action of the alkaloid     

Do prostaglandins mediate the somatostatin preventive effect on gastric lesion?

Summary The inhibition of endogenous prostaglandin synthesis by indomethacin treatment blocks the somatostatin preventive effect on the gastric lesions induced in a stress model and has no preventive effect on an intragastric distension model.     

The occurrence and physiological functions of melatonin in the most primitive eumetazoans,the planarians

Asexual planarians of the speciesDugesia dorotocephala exhibit a distinct circadian rhythm of fissoning (asexual reproduction) under the influence of normal photoperiod; fissioning occurs only at night. This rhythm is broken down by continuous illumination, continuous darkness or by decapitation. The fissioning rate increases when planarians are exposed to light for less than 1 hour/day or when they are decapitated. Fissioning of decapitated planarians is suppressed by continuous treatment with melatonin, whereas fissioning resumes when these are returned to normal culture water. Interestingly, fissioning occurs at night when decapitates are treated with melatonin in the daytime, while it is observed in the daytime with night-time melatonin treatment. Endogenous melatonin was detected by HPLC and RIA. The endogenous melatonin level is always higher in those heads collected in the scotophase than in those collected in the photophase. A type of neurosecretory cell, which may synthesize melatonin, is found in the assembly of photoreceptor cells.     

The effect of hog gastrin on gastric secretion in chronic gastric fistula rats

Résumé L'action de la gastrine de porc a été étudiée chez des rats mâles munis de fistules gastriques. La gastrine était injectée par voie s.c. à des doses de 1–2 ml: 1 ml équivalant à l'activité de 10 g de muqueuse de porc. Le volume de suc gastrique, le volume de suc gastrique par 100 g, l'acidité totale et le débit d'acide accusèrent une pointe dans la première h, alors que la concentration en acide atteignit son maximum vers la troisième h. Le débit de la pepsine diminua entre la troisième et la cinquième h et augmenta légèrement entre la cinquième et la sixième h.

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This research was supported in part by grants from the National Science Foundation (No. GB 6105) and from the AMA ERF, to J. H. T. — Dr.Robitscher of Ayerst Laboratories kindly supplied the ICI-50123.     

The effect of nicotine on ethanol-induced gastric ulcers in rats

Nicotine, in concentrations of 5 and 25 micrograms/ml drinking water, given ad libitum for 10 days, dose-dependently increased lesion formation and worsened ethanol-induced ulceration in rat stomachs. Daily fluid intake and b.wt gain were not adversely affected by nicotine pretreatment.     

N-ethylmaleimide antagonizes stress-induced gastric ulcers in rats

Summary N-ethylmaleimide (NEM) 10 or 25 mg/kg b.wt, given s.c. 20 min beforehand, dose-dependently and significantly antagonizes the severity of gastric glandular ulcers produced by restraint at 4°C (stress) for 2 h. These findings suggest that reduced activity of endogenous nonprotein sulfhydryl substances in gastric tissue does not worsen stress-induced ulceration in rat stomachs, unlike the deleterious effect its depletion is claimed to have on ethanol-evoked gastric mucosal damage. Thus, decreased SH activity appears not to play a role in the aetiology of mucosal ulcers due to stress.     

Development of melatonin rhythm in the pineal gland and eyes of chick embryo

A melatonin rhythm was observed in the pineals of 18-day-old chick embryos incubated under a light-dark regime of 186 h. A low pineal melatonin content was found during the light phase of the day. Concentrations started to increase 2 h after dark onset and reached maximum levels after 4 h of darkness. The amplitude of the pineal melatonin rhythm increased considerably after 2 days and night-time concentrations in 20-day-old embryos were more than 5 times higher than in 18-day-old ones. Significant day/night differences in melatonin production were found both in pineals and eyes. Exposure of eggs to 1 h of light during the dark period decreased the high melatonin concentrations in the eyes but not in the pineals of the 20-day-old chick embryo. The results suggest that in this precocial bird at least part of the circadian system may already operate during embryonic life.     

The contribution of extrapineal sites of melatonin synthesis to circulating melatonin levels in higher vertebrates

While the production of melatonin in higher vertebrates occurs in other organs and tissues besides the pineal, the contribution of extrapineal sites of melatonin synthesis such as the retina, the Harderian glands and the gut to circulating melatonin levels is still a matter of debate. The amount of melatonin found in the gastrointestinal tract is much higher than in any other organ including the pineal and the gut appears to make a significant contribution to circulating melatonin at least under certain conditions. The gut has been identified to be the major source of the elevated plasma concentrations of melatonin seen after tryptophan administration and of the changes of circulating melatonin level induced by the feeding regime. Whereas the circadian and circannual fluctuations of the concentration of melatonin in the blood seem to be triggered by changes of the photoenvironment and its effect of pineal melatonin formation, basal daytime melatonin levels and the extent of their elevation at nighttime appear to be additionally controlled by nutritional factors, such as the amount and the composition of ingested food and therefore availability of tryptophan as a rate-limiting precursor of melatonin formation by the enterochromaffin cells of the gastrointestinal tract.     

The effect of chlorpromazine on the adrenal gland in rats with brain stem lesions

Resumen Lesiones de la formación reticulada mesencefálica (FRM) provocan una caída significativa del ácido ascórbico supprarrenal (AAS). La clorpromazine (CPZ) provoca un aumento significativo del AAS. La administración de CPZ a ratas con lesión en FRM es incapaz de restablecer los niveles de AAS.     

The effect of chronic heat stress on cortisol levels in the antarctic fishPagothenia borchgrevinki

Radioimmunoassay was used to determine levels of the stress-inducible glucocorticoid, cortisol, circulating in the plasma of the extremely stenothermal Antarctic fishPagothenia borchgrevinki at rest and after heat stress. Fish sampled immediately after capture (–1.9°C) had low cortisol levels (10.4±1.4 ng ml^–1, mean±SEM) as did fish which were laboratory rested for 3 days. Sudden exposure to 5°C (48h) resulted in a peak cortisol value after 3 h (69.9±6.8 ng ml^–1) whereas exposure to 8°C (6h) resulted in a peak value after 1 h (73.5±8.0 ng ml^–1). At both temperatures levels remained significantly elevated (p<0.05) for the entire period of exposure. Increased temperature also resulted in a significant change in haemoglobin, haematocrit and mean cell haemoglobin concentration (MCHC) (p<0.05). Plasma lactate was significantly elevated only after exposure to 8°C (p<0.05). Plasma cortisol levels fromP. borchgrevinki are reported here for the first time and show this cryopelagic Antarctic species to have an unusual hormonal stress profile.     

Differential displacement of cells from the median eminence into the arcuate nucleus during puberty. Effects of melatonin administration

Summary A displacement of catecholaminergic-positive and catalase-containing cells from the median eminence into the arcuate nucleus at puberty has been described previously. This study reports on the displacement phenomena after postnatal administration of melatonin. Catalase-positive cells undergo a delayed displacement from the median eminence into the arcuate nucleus. However, part of this cell population lags behind within the median eminence. This differential reaction of cell displacement by catalase-positive cells is considered as a special reaction of these cells to melatonin administration.     

Development of post-hatching melatonin rhythm in zebra finches (Poephila guttata)

We examined levels of melatonin in the pineal, eyes and plasma over a 24 h period during development in the altricial zebra finch. Beginning as early as 2 days after hatching there was a distinct 24 h rhythm in melatonin in the pineal and plasma. Beginning at day seven after hatching there was also a 24 h rhythm present in the eyes. In the pineal and eyes the amplitude of the 24 h rhythm increased with age. In contrast, the amplitude of the plasma melatonin rhythm at 2 days was already within the range of adults and did not increase with age. These results confirm and expand earlier findings in the European starling and parallel those from precocial birds indicating that the circadian system is already competent at or shortly after hatching even in atricial birds.     

Hepatic glucose signals vagally modulate the cyclicity of gastric motility in rats

The cyclicity and intensity of gastric motlity were examined following glucose injection into the portal vein with an intragastric balloon in anesthetized rats. Enhanced gastric motility caused by insulin administration was influenced by 4 mM glucose (25 l) injected into the portal vein; glucose provoked a shift in the cyclicity power spectrum without any change in intensity. The peak power spectrum shifted from 4.0–5.0 cpm to 2.0–3.0 cpm. Hepatic branch vagotomy abolished the response.The results suggest that glucose signals in the hepatic vagal branch modulate the cyclicity of gastric motiligy.     

Participation of ACTH1–10 and ACTH4–10 on the melatonin modulation of benzodiazepine receptors in rat cerebral cortex

In this study, we examined the effect of intracerebroventricular (i.c.v) injection of melatonin and/or ACTH_1–10 and ACTH_4–10 on [³H]flunitrazepam binding sites in the cerebral cortex of hypophysectomized rats. Hypophysectomy increased the B_max (maximum number of binding sites) of benzodiazepine (BNZ) receptors for at least 7 days after surgery, without changing K_D (dissociation constant). The i.c.v. injection of melatonin to hypophysectomized rats significantly increased B_max, whereas the same doses of melatonin were ineffective in sham-operated animals. In both cases, K_D values were unchanged. The i.c.v injection of ACTH_1–10 to hypophysectomized animals significantly increased B_max, an effect that was enhanced by simultaneous i.c.v. injection of ACTH_1–10+melatonin, reaching higher values of B_max than the i.c.v. injection of these hormones individually. No significant changes in K_D values were found after ACTH_1–10 and/or melatonin administration. However, the i.c.v. injection of ACTH_4–10 to hypophysectomized rats did not change B_max, although it significantly increased K_D values, indicating a decrease in the BNZ binding affinity. Melatonin injection counteracted this effect of ACTH_4–10, returning K_D to the control value. Moreover, although the lower dose of i.c.v. melatonin used, 10 ng, was unable to modify B_max of BNZ binding in the ACTH_4–10-injected group, the higher dose, 20 ng, significantly increased B_max. The results suggest that these ACTH-derived peptides can modulate the effect of melatonin on brain benzodiazepine receptors.     

Exogenous melatonin accelerates re-entrainment: Attenuation of the circadian rhythm of metabolic rate in the canary,Serinus canaria

Administration of melatonin in the drinking water (200 g/ml in 1% ethanol) decreased the time of re-entrainment of the circadian rhythm of the metabolic rate (measured as oxygen uptake) of domestic canaries (Serinus canaria) after 10-h delay phase shifts of the light-dark (LD) cycle by 1.3 days on average. Associated with faster re-entrainment, the amplitude of the metabolic rhythm was attenuated by 46% on, average on the first day after the shift as compared with about 25% in the controls. After re-entrainment, the amplitude of the metabolic rhythm during melatonin administration was about 23% lower than in the controls. The minimum resting metabolic rate increased by ca 5% on average during treatment with melatonin. The results are consistent with the hypothesis that constant high plasma levels of melatonin act on higher levels of the circadian oscillatory system rather than by directly affecting peripheral or central photoreceptors.     

Clinical aspects of the melatonin action: impact of development,aging, and puberty,involvement of melatonin in psychiatric disease and importance of neuroimmunoendocrine interactions

During the last decade we have learned much on physiological changes in the secretion of the pineal hormone melatonin (MLT) in man. Reportedly, there is little or no MLT secreted before age 3 months. Then MLT production commences, becmes circadian, and reaches highest nocturnal levels at the age of 1–3 years. During all of childhood nocturnal peak levles drop progressively by 80% until adult levels are reached. This alteration appears to be the consequence of increasing body size in face of constant MLT production during childhood. The biological significance of this MLT alteration is presently unknown. Because of conceptual considerations, major depressive syndrome (MDS) and seasonal affective disorder (SAD) have been in the focus of pineal research for several years. Although in these disorders alterations in MLT levels could not be substantiated, light therapy, a consequence of this research, was discovered as an effective treatment for SAD and perhaps for MDS. In addition, there is some recent evidence for low MLT levels in schizophrenia. Finally, the potential effect of MLT in neuroimmunoendocrine interactions is presently explored. Reportedly, in vitro studies and animal experiments give evidence for a modulatory role of MLT in the immune response. However, the exact way of this possible action of MLT remains to be clarified. Clinical studies are too scant for a meaningful estimation of MLT's involvement in human neuroimmunoendocrine interactions.     

The influence of peripheral or central administration of ondansetron on stress-induced gastric ulceration in rats

Ondansetron (0.08, 0.15 or 0.3 mg/kg) injected s.c., every 12h with the fourth dose given 0.5 h before experiments, dose-dependently lessened gastric glandular mucosal ulceration produced by cold-restraint stress for 2h. When given intracerebrally (i.c.) (0.1, 0.5 or 1g), using the same treatment regimen, infusion of ondansetron 1 g into the nucleus amygdaloideus centralis decreased stress-evoked ulcers; in contrast, injection of the same dose into the nucleus accumbens intensified these lesions. The associated stress-induced stomach wall mast cell degranulation was unaffected by all s.c. or i.c. doses of ondansetron. Pretreatment with disodium cromoglycate i.p. alone, or concurrently with ondansetron s.c., prevented not only ulceration but also mast cell degranulation. 5-Hydroxytryptamine₃ receptor antagonism appears to inhibit stress-evoked ulcers mainly by blocking the peripheral effects of the amine after its release from the gastric mucosal mast cells.