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     

Nicotine and ascorbic acid effects on cold-restraint ulcers in rats

Summary Rats were orally administered 1-ascorbic acid, nicotine, 1-ascorbic acid and nicotine, or distilled water for 10 days. Following this treatment they were fasted for 24 h and then restrained in a cold environment for 2h. Nicotine alone produced significantly more gastric ulcers than any other treatment. 1-Ascorbic acid increased ulceration relative to controls. The combined effects of 1-ascorbic acid and nicotine resulted in reduced ulcer incidence and severity. It appears that 1-ascorbic acid and nicotine do not act synergistically to augment stress-induced gastric ulcer. Supported by Natural Sciences and Engineering Research Council of Canada grant No. A 6312.     

Evidence for an olfactory receptor which responds to nicotine — nicotine as an odorant

Summary The tobacco alkaloid (S)(–)-nicotine, when applied as a vapour to an in vitro head preparation, stimulates the olfactory epithelium in three strains of rats and to a lesser extent in two strains of mice. The electro-olfactogram (EOG) generated by nicotine has similar characteristics to the EOGs produced by known odorants. The nicotine EOG increases with increasing concentration of nicotine vapour (1–100 nM) applied to the olfactory epithelium.Differential reduction of the nicotine EOG by the lectin concanavalin A is seen in Wistar and Lister Hooded rats. The reduction of the nicotine EOG by concanavalin A is prevented by adding alpha-methyl-D-mannoside to the lectin superfusion medium. This suggests that there is a glyco-moiety associated with at least one olfactory receptor responding to nicotine.Our results suggest that rat olfactory epithelium has receptor sites for nicotine. Nicotine is an unusual compound because it shows both odorant and pharmacological properties.22 September 1986     

Evidence for an olfactory receptor which responds to nicotine--nicotine as an odorant

The tobacco alkaloid (S)(-)-nicotine, when applied as a vapour to an in vitro head preparation, stimulates the olfactory epithelium in three strains of rats and to a lesser extent in two strains of mice. The electro-olfactogram (EOG) generated by nicotine has similar characteristics to the EOGs produced by known odorants. The nicotine EOG increases with increasing concentration of nicotine vapour (1-100 nM) applied to the olfactory epithelium. Differential reduction of the nicotine EOG by the lectin concanavalin A is seen in Wistar and Lister Hooded rats. The reduction of the nicotine EOG by concanavalin A is prevented by adding alpha-methyl-D-mannoside to the lectin superfusion medium. This suggests that there is a glyco-moiety associated with at least one olfactory receptor responding to nicotine. Our results suggest that rat olfactory epithelium has receptor sites for nicotine. Nicotine is an unusual compound because it shows both odorant and pharmacological properties.     

Fluorogenic amines in the notochords of chick embryos treated by cholinergics]

The investigation of 3 day old notochords by the fluorescence method of Falck and Owman showed an increase of the fluorescence after treatment of the chick embryos at 48 hrs of incubation, with nicotine sulfate or carbachol. The addition of norepinephrine or L-Dopa emphasized the formaldehyde induced fluorescence. The simultaneous treatment with a cholinergic agent and atropine, propranolol or reserpine decreased or suppressed the fluorescence. These results demonstrate the existence of a relationship between the treatment with a cholinergic agent and the amount of chordal biogenic amines.     

Stimulation of gastric secretion by prostaglandin F2 alpha in rats.

In rats with chronic gastric fistulas, prostaglandin F2 alpha stimulated the gastric acid secretion in graded doses of 50, 100, 200 and 400 microgram/kg b.wt, while higher doses above 1 mg/kg b.wt tended to inhibit significantly. The gastric antisecretory effect of prostaglandin E1 could not be altered or modified by subsequent treatment of prostaglandin F2 alpha, while the latter alone without any prior treatment of the former, stimulated output of gastric juice, HCl and pepsin without significantly affecting the concentration of these components.     

Spatial variation in response to odorants on the rat olfactory epithelium

We have measured the electro-olfactogram produced by four odorants, nicotine, i-pentyl acetate, i-pentanoic acid and cineole from twelve positions on an in vitro preparation of rat olfactory tissue. Each odorant shows a different pattern of response over the twelve positions which can be explained by differences in olfactory receptor populations between regions of the rat olfactory epithelium. The result for nicotine is further evidence that there are olfactory receptors which are stimulated by nicotine when it is presented as a vapour.     

Untersuchungen über die Nikotinbildung des Tabaks

Summary During germination the tobacco seedling produces nicotine from proteins accumulated in the seed. Later on the nicotine formation of the growing tobacco plant is dependent on the protein synthesis in its root. The comparison of theprotein production by the tobacco root with thenicotine content of the whole plant shows an interesting parallelism.     

Developmental nicotine exposure induced alterations in behavior and glutamate receptor function in hippocampus

In the developing brain, nicotinic acetylcholine receptors (nAChRs) are involved in cell survival, targeting, formation of neural and sensory circuits, and development and maturation of other neurotransmitter systems. This regulatory role is disrupted when the developing brain is exposed to nicotine, which occurs with tobacco use during pregnancy. Prenatal nicotine exposure has been shown to be a strong risk factor for memory deficits and other behavioral aberrations in the offspring. The molecular mechanisms underlying these neurobehavioral outcomes are not clearly elucidated. We used a rodent model to assess behavioral, neurophysiological, and neurochemical consequences of prenatal nicotine exposure in rat offspring with specific emphasis on the hippocampal glutamatergic system. Pregnant dams were infused with nicotine (6 mg/kg/day) subcutaneously from the third day of pregnancy until birth. Results indicate that prenatal nicotine exposure leads to increased anxiety and depressive-like effects and impaired spatial memory. Synaptic plasticity in the form of long-term potentiation (LTP), basal synaptic transmission, and AMPA receptor-mediated synaptic currents were reduced. The deficit in synaptic plasticity was paralleled by declines in protein levels of vesicular glutamate transporter 1 (VGLUT1), synaptophysin, AMPA receptor subunit GluR1, phospho(Ser845) GluR1, and postsynaptic density 95 (PSD-95). These results suggest that prenatal nicotine exposure by maternal smoking could result in alterations in the glutamatergic system in the hippocampus contributing to the abnormal neurobehavioral outcomes.     

Mediation by nitric oxide of neurally-induced human cerebral artery relaxation

Human cerebral artery strips relaxed in response to non-adrenergic, non-cholinergic vasodilator nerve stimulation by electrical pulses or nicotine. The relaxation response was abolished by treatment with N^G-nitro-L-arginine, a nitric oxide synthase inhibitor; the inhibitory effect was reversed by L-, but not D-, arginine. Nitric oxide-induced relaxation was unaffected. These findings support the hypothesis that nitric oxide plays a crucial role, possibly as neurotransmitter, in transmitting information from vasodilator nerve to smooth muscle in human cerebral arteries.     

Depression of experimental gastric ulcers and acute pancreatitis in rats treated by 5-azacytosine, 5-azacytidine and their N-methyl derivatives

5-Azacytosine, 1-methyl-5-azacytosine and 5-azacytidine administered to rats with a ligated pylorus block gastric secretion, gastric acidity, the extent of hemorrhage and the number and size of gastric defects. The same drugs also depress the development of experimental acute pancreatitis mediated in rats by interstitial administration of 7.5% natrium cholate into the pancreas in vivo. The drugs affected the amount of abdominal fluid and 6 h after the treatment the pathological changes were significantly decreased.     

Depression of experimental gastric ulcers and acute pancreatitis in rats treated by 5-azacytosine, 5-azacytidine and their N-methyl derivatives

Summary 5-Azacytosine, 1-methyl-5-azacytosine and 5-azacytidine administered to rats with a ligated pylorus block gastric secretion, gastric acidity, the extent of hemorrhage and the number and size of gastric defects. The same drugs also depress the development of experimental acute pancreatitis mediated in rats by interstitial administration of 7.5% natrium cholate into the pancreas in vivo. The drugs affected the amount of abdominal fluid and 6 h after the treatment the pathological changes were significantly decreased.     

Cytoprotective effects of acidosis via heat shock protein HSP27 against the anticancer drug doxorubicin

Drug resistance continues to be a stumbling block in achieving better cure rates in several cancers. Doxorubicin is commonly used in treatment of a wide range of cancers. The aim of this study was to look into the mechanisms of how low ambient pH may contribute to down-regulation of apoptotic pathways in a gastric tumour cell line. Low pH culture conditions were found to dramatically prolong cell survival after doxorubicin treatment, an effect that was in part reversed by co-incubation with the specific p38 mitoge-activated protein kinase (MAP kinase) inhibitor SB203580, only mildly inhibited by blockade of the multi-drug resistance 1 (MDR1) transporter, but completely abolished by siRNA-mediated knockdown of the heat shock protein 27 (HSP27). In conclusion, acidic pH causes less accumulation of cytotoxic drug in the nucleus of adeno gastric carcinoma (AGS) cells and HSP27-dependent decrease in FasR-mediated gastric epithelial tumour cell apoptosis.     

Spatial variation in response to odorants on the rat olfactory epithelium

Summary We have measured the electro-olfactogram produced by four odorants, nicotine, i-pentyl acetate, i-pentanoic acid and cineole from twelve positions on an in vitro preparation of rat olfactory tissue. Each odorant shows a different pattern of response over the twelve positions which can be explained by differences in olfactory receptor populations between regions of the rat olfactory epithelium.The result for nicotine is further evidence that there are olfactory receptors which are stimulated by nicotine when it is presented as a vapour.     

Microsatellite instability in gastric cancer: molecular bases,clinical perspectives,and new treatment approaches

Gastric cancer is one of the most aggressive malignancies, with limited treatment options in both locally advanced and metastatic setting, resulting in poor prognosis. Based on genomic characterization, stomach tumour has recently been described as a heterogeneous disease composed by different subtypes, each of them with peculiar molecular aspects and specific clinical behaviour. With an incidence of 22% among all western gastric tumour cases, stomach cancer with microsatellite instability was identified as one of these subgroups. Retrospective studies and limited prospective trials reported differences between gastric cancers with microsatellite stability and those with instability, mainly concerning clinical and pathological features, but also in regard to immunological microenvironment, correlation with prognostic value, and responses to treatment. In particular, gastric cancer with microsatellite instability constitutes a small but relevant subgroup associated with older age, female sex, distal stomach location, and lower number of lymph-node metastases. Emerging data attribute to microsatellite instability status a favourable prognostic meaning, whereas the poor outcomes reported after perioperative chemotherapy administration suggest a detrimental role of cytotoxic drugs in this gastric cancer subgroup. The strong immunogenicity and the widespread expression of immune-checkpoint ligands make microsatellite instability subtype more vulnerable to immunotherapeutic approach, e.g., with anti-PD-L1 and anti-CTLA4 antibodies. Since gastric cancer with microsatellite instability shows specific features and clinical behaviour not overlapping with microsatellite stable disease, microsatellite instability test might be suitable for inclusion in a diagnostic setting for all tumour stages to guarantee the most targeted and effective treatment to every patient.     

Noradrenalin-Freisetzung aus isolierten Hypothalamus-Vesikeln

Summary Potassium and sodium from isolated pig hypothalamic vesicles cause a dose dependent release of noradrenaline. The releasing effect of nicotine is less pronounced than that of acetylcholine. No addition of the effects could be observed by simultaneous incubation with calcium and potassium or calcium and nicotine. The effect of potassium is abolished by tetracain.

---

---

Ausgeführt mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Do prostaglandins mediate the somatostatin preventive effect on gastric lesion?

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.     

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 effect of nicotine on blood pressure in the genetically hypertensive mouse

Summary Mice genetically selected for high and low blood pressure were exposed to nicotine via a single injected dose or addition to drinking water for 52 weeks. In the acute study, the response of mice with high blood pressure was a statistically significant increase in blood pressure. In the chronic study the pattern of response to nicotine ingestion was similar for mice with high blood pressure and those with low. Both lines responded with an increase in blood pressure after 6 weeks followed by a decrease to below baseline blood pressure at 12 weeks.This research was supported in part by an allocation from the General Research Fund of the University of Kansas.     

Chronic effects of nicotine on gastric secretion in vagotomized rats

Résumé La sécrétion gastrique a été mesurée dans des rats mâles avec ligature pylorique de deux heures, après 14 jours d'injections sous-cutanées de nicotine ou de NaCl. Les résultats de l'administration de nicotine furent une augmentation du volume du suc gastrique, de la production d'acide et de la production de pepsine. La vagotomie abdominale bilatérale a prévenu la stimulation gastrique secreteuse, provoquée par la nicotine.