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PubMed1987

Induction of hepatic metallothionein following administration of urethane.

Induction of hepatic metallothionein (MT) by urethane (ethyl carbamate) was characterized. Male CF-1 mice were treated with urethane (0, 0.5, 1.0, 1.5, and 2 g/kg; ip) and 18 hr later hepatic MT concentrations were determined with the Cd-hemoglobin radioassay. Urethane (1 g/kg and higher) significantly increased hepatic MT levels, resulting in a 14-fold increase after 2 g/kg. Time-course experiments indicated that MT levels were increased significantly at 6 hr after administration of urethane (1.5 g/kg) and reached a maximum between 12 and 24 hr. Gel filtration, anion-exchange chromatography, and ultraviolet spectral analysis were used to characterize the protein induced by urethane. Pretreatment with actinomycin-D prevented induction of MT by urethane. Administration of equimolar dosages (20 mmol/kg) of urethane, N-hydroxyurethane, and methyl carbamate indicated that urethane and N-hydroxyurethane induce MT but that methyl carbamate does not. MT induction was also not observed with other commonly used anesthetics (pentobarbital and phenobarbital). In conclusion, urethane induces hepatic MT but this effect is not related to its anesthetic action, nor is it a common property of all carbamates.

Anesthetics↗
PubMed2005

Inhibition of urethane-induced genotoxicity and cell proliferation in CYP2E1-null mice.

Urethane is a multi-site animal carcinogen and was classified as "reasonably anticipated to be a human carcinogen." Urethane is a fermentation by-product and found at appreciable levels in alcoholic beverages and foods such as bread and cheese. Recent work in this laboratory demonstrated for the first time that CYP2E1 is the principal enzyme responsible for urethane metabolism. The current studies were undertaken to assess the relationships between CYP2E1-mediated metabolism and urethane-induced genotoxicity and cell proliferation as determined by induction of micronucleated erythrocytes (MN) and expression of Ki-67, respectively, using CYP2E1-null and wild-type mice. Urethane was administered at 0 (vehicle), 1, 10, or 100mg/kg/day (p.o.), 5 days/week for 6 weeks. A significant dose-dependent increase in MN was observed in wild-type mice; however, a slight increase was measured in the MN-polychromatic erythrocytes in CYP2E1-null mice treated with 100mg/kg. A significant increase in the expression of Ki-67 was detected in the livers and the lungs (terminal bronchioles, alveoli, and bronchi) of wild-type mice administered 100mg urethane/kg in comparison to controls. In contrast, CYP2E1-null mice administered this dose exhibited negligible alterations in Ki-67 expression in the livers and lungs compared to controls. Interestingly, while Ki-67 expression in the forestomach decreased in wild-type mice, it increased in CYP2E1-null mice. Subsequent comparative metabolism studies demonstrated that total urethane-derived radioactivity in the plasma, liver, and lung was significantly higher in CYP2E1-null versus wild-type mice and un-metabolized urethane constituted greater than 83% of the radioactivity in CYP2E1-null mice. Un-metabolized urethane was not detectable in the plasma, liver, and lung of wild-type mice. In conclusion, these data demonstrated that CYP2E1-mediated metabolism of urethane, presumably via epoxide formation, is necessary for the induction of genotoxicity, and cell proliferation in the liver and lung of wild-type mice.

Animals↗
PubMed2002

Immune stimulation in urethane-exposed pregnant mice increases expression level of spleen leukocyte genes for TGFbeta3 GM-CSF and other cytokines that may play a role in reduced chemical-induced birth defects.

For unknown reasons, activation of the maternal immune system in mice reduces morphologic defects caused by diverse teratogenic agents. Such immune stimulation of the maternal animal has been correlated with altered cytokine mRNA transcripts in the placenta (e.g., TGFbeta2) as well as in fetal target tissues of the teratogen (e.g., TNFalpha in fetal heads of cyclophosphamide-exposed pregnant mice). The teratogen urethane was reported to down-regulate cell cycle and apoptotic regulatory genes in fetal mouse heads that displayed cleft palate, an effect that was also reversed by maternal immune stimulation. The molecular mediators of the above phenomena have not been identified, however proteins synthesized and released by activated maternal immune cells have been suggested. The present studies therefore evaluated the effects of maternal immune stimulation in urethane-exposed mice on thymus and spleen leukocyte populations, in an attempt to identify events that may correlate with protection against birth defects. Immune stimulation did not change the hypocellularity of the thymus nor the altered T cell differentiation caused by urethane. A limited and transient increase in splenic leukocyte number, including increased T and B lymphocytes and macrophages, was caused by immune stimulation and was not felt to play a significant role in reduced morphologic defects. Urethane treatment caused down-regulated expression of numerous genes involved in cell-cycle control, while maternal immune stimulation caused comparative up-regulation of many of these genes. Coordinate shifts in gene expression by treatment were evaluated using principal component analysis, which identified several growth factor genes that were differentially expressed in mice receiving urethane alone as compared to urethane plus immune stimulation. Up-regulated expression of TGFbeta3 and GM-CSF genes, in particular, was observed in leukocytes of urethane-exposed mice receiving immunostimulation. Interestingly, the cytokine products of these two genes were recently suggested as growth factors that may be related to reduction of fetal defects caused by teratogens. Genes for growth factors IGF-I, IGF-II and IL-2 were also identified as differentially expressed in urethane vs. urethane+immune stimulation mice, suggesting that these proteins should be considered for a potential contributing effect to reduced birth defects caused by immunostimulation.

Abnormalities, Drug-Induced↗
PubMed1986

Genetic variation in the proliferation of murine pulmonary type II cells: basal rates and alterations following urethan treatment.

Susceptibility to urethan-induced pulmonary tumorigenesis varies among inbred strains of mice. A genetic basis for this variation was sought using three strains with widely differing tumor multiplicities after urethan treatment. Twenty-one mice from each of strains A/J (high susceptibility), BALB/cByJ (intermediate susceptibility; hereafter called cBy), and C57BL/6J (low susceptibility; hereafter called B6) were treated i.p. with 1 mg urethan/g body weight, and sacrificed at 0 (no urethan), 12, 24, 36, 48, 65, and 80 days after treatment (three mice per strain per time point). Each mouse was given 1 muCi [3H]thymidine/g body weight 45 min before sacrifice. Lungs were processed for autoradiography, and labeling indices were independently determined for non-tumor-associated type II cells and for tumor cells (most tumors arise from alveolar type II pneumocytes in A/J mice). Three categories of proliferative differences were found. First, statistically significant differences (P less than 0.05) among all strains were found for type II cell labeling indices in untreated mice, and these differences persisted for 65 days after urethan treatment. Proliferative rates were highest in A/J mice and lowest in B6 mice, while cBy mice were intermediate. Secondly, the peak of type II cell labeling occurred 12 days following urethan in strains A/J and cBy, but at 24 days in B6 mice. This difference is consistent with the fact that tumors were observed earlier following urethan treatment in A/J and cBy mice (at 36 days) than in B6 mice (at 48 days). Finally, the labeling indices in A/J and B6 tumors were high at first (6 and 4%) and then declined to 1-1.5% by 80 days after urethan treatment, while cBy tumor labeling indices remained at about 1.5% throughout the experimental period. These results suggest that the variation in susceptibility to urethan-induced lung tumorigenesis among different strains of mice is related to the normal basal rates of lung mitoses in these strains. Mice may be particularly sensitive to urethan during cell division, making strains with a higher rate of mitosis more susceptible to tumorigenesis.

Animals↗
PubMed1981

Inhibition of the activity of mouse natural killer cells by urethan.

The effect of the carcinogen urethan on the natural killer (NK) activity of spleen cells from inbred A/J mice was studied. Urethan (1 mg/g) inoculated into 6- to 8-week-old A/J mice produced considerable depression of cytotoxic activity of spleen cells against YAC-1 or RL male 1 tumor cells. This effect was biphasic. Initial depression of NK activity was observed 1 day after urethan treatment, reactivity normalized at 4 days, and then a second, more profound depression was seen around 7-8 days, which persisted for 14-18 days. In contrast, lymphoproliferative responses of spleen cells to mitogens were only transiently depressed after urethan treatment and were in the normal range during the second period of marked depression of NK activity. Urethan appeared to have an even more profound effect on NK activity when given to very young mice (5-17 days old). After one or two injections of urethan, very low splenic NK activity was found 6 and 7 weeks later. The carcinogenic effects of urethan were also more striking in these young recipients, with multiple tumors observed in the lungs at the time of cytotoxicity testing. Inoculation of adult urethan-treated mice with the interferon inducer polyinosinic-polycytidylic acid, boosted NK activity to the same extent as seen with normal mice, which suggested that pre-NK cells are resistant to the effects of urethan. The present data agree with the hypothesis that the ability of a chemical to depress NK cell activity is an important factor in its carcinogenic activity.

Age Factors↗
PubMed1990

Chronic ethanol intake and reduction of lung tumours from urethane in strain A mice.

Combinations of ethanol and urethane were added to the drinking-water of female strain A/Ph mice for 12 wk, at the end of which the animals were killed. Urethane concentrations were 0, 200, 500 and 1000 ppm and ethanol concentrations, 0, 5, 10 and 20% (v/v). All possible combinations of these urethane and ethanol concentrations were tested. Urethane induced primary lung adenomas in all treated mice in a dose-dependent manner. An average of 71 +/- 15 tumours/mouse were found, when the animals were killed, after treatment with 1000 ppm urethane for 12 wk. Ethanol alone did not alter the background incidence of tumours and produced only marginal hepatotoxicity. The tumour yields induced by urethane treatment were greatly reduced by simultaneous treatment with ethanol. The effect of ethanol was independent of urethane dose. When the concentrations of ethanol in the drinking-water were 20 and 10% the incidences of lung adenomas induced by urethane were reduced by about two-thirds and one-half, respectively. The effect of 5% ethanol, if any, was not statistically significant.

Adenoma↗
PubMed1991

Urethan (ethyl carbamate) is an effective promoter of 7,12-dimethylbenz[a]anthracene-induced carcinogenesis in mouse skin two-stage experiments.

Groups of hairless mice were painted with urethan alone, with the complete carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) alone, and with an initiating dose of DMBA followed by continual treatment with urethan or with the promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). The animals were examined once a week for an appropriate time period. Malignant and non-malignant skin tumors were registered and classified. Lung adenomas and other internal tumors were also counted. The results show that all types of treatment produced skin tumors, some of which were malignant. When urethan was used lung adenomas also appeared, along with a few other tumors. The results show that a 10% solution of urethan in acetone is a significant promoter, showing synergistic increase of DMBA-induced skin tumors, but urethan is not as strong a promoter as 10 nmol TPA. Urethan is said to be the pure initiator of skin carcinogenesis. Previously the author has shown that urethan alone is a complete carcinogen and here it is shown that it is also a promoter. Hence, the current hypothesis of urethan as a pure initiator in skin carcinogenesis has been disproved.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

Urethane and contraction of vascular smooth muscle.

1 In vitro studies were undertaken on rat aortic strips and portal vein segments in order to determine whether or not the anaesthetic, urethane, can exert direct actions on vascular smooth muscle. 2 Urethane was found to inhibit development of spontaneous mechanical activity. This action took place with a urethane concentration as little as one tenth of that found in anaesthetic plasma concentratios, i.e., 10(-3) M. 3 Urethane (10(-3 to 10(-1) M) dose-dependently attenuated contractions induced by adrenaline, angiotensin and KCl. These inhibitory actions were observed with urethane added either before or after the induced contractions. 4 Ca2+-induced contractions of K+-depolarized aortae and portal veins were also attenuated, dose-dependently, by urethane. 5 All of these inhibitory effects were completely, and almost immediately, reversed upon washing out the anaesthetic from the organ baths. 6 A variety of pharmacological antagonists failed to mimic or affect the inhibitory effects induced by urethane. 7 These data suggest that plasma concentrations of urethane commonly associated with induction of surgical anaesthesia can induce, directly, relaxation of vascular muscle.

Angiotensin II↗
PubMed1988

Hazards of urethane (ethyl carbamate): a review of the literature.

Urethane (ethyl carbamate) is used alone or in combination with other drugs to produce anaesthesia in laboratory animals. Although originally studied as a potential phytocide, urethane demonstrated antineoplastic properties when administered to rats with the Walker rat carcinoma 256. Subsequent trials in humans led to its use as a chemotherapeutic agent for various leukaemias. Mice develop pulmonary adenomas earlier in life and at a higher incidence following urethane administration. Urethane's carcinogenic influence is greater in neonatal mice; it also has a transplacental influence in mice. In rats, urethane increases the incidence of pulmonary adenomas, Zymbal Gland tumours, and a variety of other neoplasms. Urethane is absorbed sufficiently from the skin of laboratory animals to produce a transient narcosis. The carcinogenic effect appears to be due to an undefined oncogenic intermediate formed in the blood. Considering the properties urethane demonstrates in animals, the safety of its use by laboratory personnel is in question. However, if appropriate guidelines are followed, urethane should continue to be a useful anaesthetic agent for laboratory animals.

Adenoma↗
PubMed1990

Suppression of the proestrus prolactin surge in the rat estrous cycle by urethane anesthesia.

Urethane-anesthetized male rats have been used for the analysis of prolactin (PRL)-releasing substances on PRL secretion. However, there are only a few reports investigating the effect of urethane anesthesia on PRL secretion in female rats. In this study, we intended to examine the effects of urethane anesthesia on PRL secretion during proestrus in the rat. Proestrus PRL surge was completely blocked when urethane was administered to rats prior to the critical period of proestrus both at doses of 1.0 g/kg and 1.5 g/kg. Additionally, urethane, at a dose of 1.5 g/kg, was also effective in blocking spontaneous ovulation. An experiment examining pituitary PRL concentration at 1800 h confirmed that urethane (1.0 g/kg) anesthesia prevents the PRL surge from the pituitary. Similarly, urethane anesthesia blocked the LH surge from the pituitary, but LH levels in the urethane-treated group were higher than those in the pentobarbital-treated group.

Anesthesia↗
PubMedDate not supplied

Inhibition of the metabolism of urethane in the mouse by dimethyl sulfoxide (DMSO).

Previous studies from this laboratory have shown that alcohols inhibit the localization of nitrosonornicotine and urethane in tissues of the mouse. Subsequent studies demonstrated that this inhibition of the localization of urethane was apparently due to an almost total inhibition of the metabolism of that compound by ethanol. We now report that dimethyl sulfoxide (DMSO) also almost completely inhibits the localization of urethane metabolites in tissues of the mouse and maintains a high concentration of urethane in blood. Since metabolism is essentially the only route of elimination of urethane in the mouse, this indicates that DMSO inhibits the metabolism of urethane. These studies lend further support to the suggestion that urethane is metabolized by either an alcohol dehydrogenase, an aldehyde dehydrogenase, or an alcohol-preferring isozyme of cytochrome P-450. These results indicate that studies on the metabolism as well as the carcinogenic activity of urethane (and possibly other chemicals) also may be affected by concurrent administration of DMSO.

Animals↗
PubMedDate not supplied

Possible hemodynamic basis to urethane anesthesia-induced reductions in renal clearance.

The hemodynamic basis of reported urethane anesthesia-induced reductions in the clearance of some renally eliminated compounds has been investigated in the laboratory rat. The use of urethane as an anesthetic in pharmacokinetic studies still persists, particularly in experiments of long duration. Using a microsphere technique, the per cent distribution of cardiac output to the kidneys, in both ip urethane- and ip Hypnorm/Hypnovel-anesthetized animals was significantly (p less than 0.01) lower than that observed in ip pentobarbital-anesthetized animals. However, the cardiac index in the Hypnorm/Hypnovel-anesthetized animals was 42% greater (p less than 0.01) than in the pentobarbital-treated animals and 86% greater (p less than 0.01) than in the urethane-treated group. Additionally, the cardiac index in the pentobarbital-anesthetized animals was significantly greater (p less than 0.01) than in the urethane-anesthetized animals. The lower cardiac index and reduced cardiac distribution to the kidneys in the urethane-treated group resulted in significant (p less than 0.01) reductions of approximately 40% in renal blood flow and glomerular filtration rate compared with the animals anesthetized with pentobarbital or Hypnorm/Hypnovel. The transport capacity of the basolateral organic anion secretory mechanism was not compromised by an ip injection of urethane, as demonstrated by p-aminohippuric acid transport studies conducted in isolated renal tubule fragments prepared from anesthetized animals. In conclusion, urethane anesthesia results in significant alterations of renal hemodynamics compared with pentobarbital and Hypnorm/Hypnovel anesthesia in the rat. For primarily renally eliminated compounds, such alterations are likely to influence pharmacokinetic data generated using this anesthetic agent.

Anesthesia↗
PubMed1981

Susceptibility of various strains of mice to urethan-induced lung tumors and depressed natural killer cell activity.

Inbred A/J, CBA/J, and C57BL/6 mice at age 7-8 weeks were inoculated with 1 mg urethan/g body weight. Three months later, 13.2, 1.8, and 0.1 tumors per lung were found in these mice, respectively. Cytotoxicity by spleen cells of normal and urethan-treated mice was analyzed in a 4-hour 51Cr release assay against YAC-1 cells. During the first 2 weeks after treatment, urethan strongly suppressed the cytotoxicity by spleen cells of A/J mice but had relatively little effect on the reactivity of spleen cells of CBA/J mice. Natural killer (NK) activity was not suppressed in urethan-treated C57BL/6 mice. The effect of urethan on natural in vivo antitumor resistance in the lungs was studied by measurement of elimination from the lungs of [125I]-deoxyuridine-labeled YAC-1 cells. Urethan caused profound and sustained suppression of in vivo NK reactivity in the lungs of A/J mice, had only a transient effect on CBA/J mice, and had no detectable effect on C57BL/6 mice. The differences in the effects of urethan on the natural antitumor resistance in the three strains of mice could not be attributed to a generally greater susceptibility of A/J mice to inhibition of NK activity, since cyclophosphamide (0.15 mg/g) equally suppressed the clearance from the lungs of the radiolabeled tumor cells in A/J, CBA/J, and C57BL/6 mice. These results indicate a positive correlation between susceptibility of A/J, CBA/J, and C57BL/6 mice to urethan-induced lung carcinogenesis and inhibition of in vitro and in vivo natural cell-mediated cytotoxicities and support the hypothesis that NK cells play a role in resistance to urethan-induced lung carcinogenesis.

Animals↗
PubMed1999

Totally implantable artificial hearts and left ventricular assist devices: selecting impermeable polycarbonate urethane to manufacture ventricles.

In the development of a new generation of totally implantable artificial hearts and left ventricular assist devices (VADs) for long-term use, the selection of an acceptable material for the fabrication of the ventricles probably represents one of the greatest challenges. Segmented polyether urethanes used to be the material of choice due to their superior flexural performance, acceptable blood compatibility, and ease of processing. However, because they are known to degrade and to be readily permeable to water, they cannot meet the rigorous requirements needed for a new generation of implantable artificial hearts and VADs. Therefore, the objective of the present study was to identify alternative polymeric materials that would be satisfactory for fabricating the ventricles, and in particular, to determine the water permeability through membranes made from four commercial polycarbonate urethanes (Carbothane PC3570A, Chronoflex AR, Corethane 80A, and Corethane 55D) in comparison to those made from two traditional polyether urethanes (Tecoflex EG80A and Tecothane TT-1074A). In addition to determining the rate of water transmission through the six membranes by exposing them to deionized water, saline, and albumin-Krebs solution under pressure and measuring the displacement of liquid by means of a recently developed capillary method, the inherent surface and chemical properties of the six membranes were characterized by SEM, contact angle measurements, FTIR, DSC, and GPC techniques. The results of the study demonstrated that the rate of water transmission through the four polycarbonate urethane membranes was significantly lower than through the two polyether urethanes. In fact the lowest values were recorded with the two Corethane membranes, and the harder type 55D polymer had a lower value (2.7 x 10(-7) g/s cm2) than the softer 80A version (3.3 x 10(-7) g/s cm2). This level of water vapor permeability, which appears to be controlled primarily by a Fickian diffusion mechanism, is between 2 and 4 times lower than that obtained with traditional polyether urethane membranes of equivalent thickness. The superior performance of the polycarbonate urethanes is likely due to the inherently lower chain mobility of the carbonate structure in the soft segment phase. In addition, the study shows that additional impermeability to water vapor can be achieved by selecting a polyurethane polymer with a high hard segment content, an aromatic rather than aliphatic diisocyanate comonomer, and a more hydrophobic surface. The use of a higher molecular weight polyurethane is not necessarily efficacious if the above requirements are not met. As expected by Raoult's Law, the study found that the use of physiological media instead of deionized water further decreases the rate of water vapor transmission. Because none of today's commercial polyurethanes are totally impervious to water vapor transmission, additional work is needed to develop permeable polymers or to apply additional treatments to existing candidates to achieve an acceptable impermeable ventricle material.

Biocompatible Materials↗
PubMed1992

Responses of barrel cortex neurons in awake rats and effects of urethane anesthesia.

A "barrel" is an interconnected network of layer IV neurons that is an important component of a functional cortical column in the whisker area of the rodent primary somatosensory cortex. The present study was undertaken in order to resolve apparently conflicting findings from single-unit studies of barrel neurons conducted in rats maintained under different anesthetic conditions. Multiunit responses to controlled deflections of mystacial vibrissae were recorded from the whisker/barrel cortex of awake, undrugged rats, and responses at the same recording site were reexamined after the animal was anesthetized with urethane. In contrast to the awake condition, stimulus-evoked responses under urethane were characterized by a large late component. Such effects were more pronounced for deflections of noncolumnar or "adjacent" whiskers than for the columnar whisker. Latencies to peak responses were virtually identical for the columnar whisker in awake and urethane states (11.9 vs 11.8 ms) but were considerably longer for adjacent whisker deflections in urethane-anesthetized animals (15.5 vs 29.0 ms). The magnitudes of adjacent whisker responses, relative to the response evoked by the columnar whisker, varied with the laminar location of the recording site in awake but not in urethane-anesthetized animals; in awake rats, receptive fields were clearly smallest in the layer IV barrels. Results in the awake condition confirm those of previous studies conducted in unanesthetized or lightly sedated animals, and data obtained with urethane are comparable to others' results in urethane-anesthetized rats. The former have important implications for how barrel cortex processes information in behaving animals.

Anesthesia↗
PubMed1983

Effects of urethan on lymphokine-producing activity of lymphocytes and on some functions of peritoneal macrophages in rats.

Effects of urethan on some functions of blood lymphocytes and peritoneal macrophages (PMs) of rats were studied in in vivo and in vitro experiments. The in vitro lymphokine (LK) producing activity of lymphocytes in the presence of specific antigen was depressed by urethan administered 1-5 days before the BCG sensitization. However, the drug injected after the BCG sensitization was not effective on the LK production. Urethan added to the cultures of previously BCG-primed lymphocytes did not influence the LK production. The sensitivity of glycogen-provoked PMs (pPM) to LK-induced activation and, at the same time, the 125I-IgG2a binding capacity as well as the EA rosette formation of the provoked PMs were depressed by urethan administered 1-5 days before the lavage of PMs. These functions of resident PMs (rPM) were not altered by the drug treatment. Urethan added to the cultures of resident or provoked PMs proved to be ineffective. These results led to the conclusions that urethan, after its in vivo metabolic conversion, causes an impairment of the macrophage functions in the inductive phase of the immune response and this event may be the crucial point in the immunosuppressive effect of urethan.

Animals↗
PubMed1994

Influences of urethane anesthesia on indomethacin-induced gastric mucosal lesions in rats. Relation to blood glucose levels.

Effects of urethane on gastric motility and mucosal ulcerogenic responses induced by indomethacin were investigated in the rat in relation to blood glucose levels (BGL) and compared with those of pentobarbital Na. Urethane (1.25 g/kg) given intraperitoneally, caused a progressive and significant rise in BGL, while pentobarbital (30 mg/kg) given intraperitoneally did not affect BGL. Subcutaneous administration of indomethacin (25 mg/kg) caused high-amplitude gastric contractions and induced hemorrhagic lesions in the stomachs of conscious rats. These lesions were significantly inhibited by urethane but not pentobarbital. Administration of urethane abolished basal gastric motility and almost completely suppressed the motility responses induced by indomethacin, while pentobarbital did not have much effect on gastric motility under basal and indomethacin-stimulated conditions. Acid secretion was significantly decreased by urethane and increased by pentobarbital. Pretreatment of the animals with yohimbine (5 mg/kg, subcutaneously) but not prazosin (0.5 mg/kg) inhibited the elevation in BGL seen after administration of urethane and allowed resumption both gastric motility and ulcerogenic responses induced by indomethacin, with less change in acid secretion. These results suggest that intraperitoneal administration of urethane prevented indomethacin-induced gastric lesions, probably by inhibiting the enhanced gastric motility response, and this effect may relate to its hyperglycemic action mediated by alpha 2-adrenoceptors. These findings also provide further evidence to support the importance of gastric motility in the pathogenesis of these lesions.

Anesthesia, General↗
PubMed1995

The effect of urethane anesthesia on evoked potentials in dentate gyrus.

We examined the effect of urethane (1000 mg/kg, followed by 50 mg/kg per h, i.v.), an anesthetic commonly used by physiologists, on evoked potentials recorded in dentate gyrus in adult Wistar rats by stimulating the ipsilateral perforant path, via chronically implanted electrodes. Urethane decreased paired-pulse inhibition. Under urethane, with paired-pulse stimulation, the ratio of the second population spike amplitude to the first increased by 11.1-20.7% at 25-60 ms interstimulus interval (n = 18, P < 0.05). At 25 ms, the proportion was 3.6 +/- 1.6 while awake, and 14.7 +/- 3.5 under urethane. Urethane depressed granule cell excitability and strength of synaptic responses. Under urethane, the ratio of the population spike amplitude obtained at 250 microA stimulation to the maximal response in the same input/output response examination decreased by 20%, and the ratio of the excitatory postsynaptic response slopes fell by 10%. These results indicate that urethane affects neurotransmission in the hippocampus, and suggest that its effect may be exerted in part on excitatory neurotransmission.

Analysis of Variance↗