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PubMedDate not supplied

Correlation of 14C-griseofulvin metabolism in rat liver microsomes, isolated perfused rat livers, and in rats with bile duct cannulas.

The metabolism of 14C-griseofulvin has been compared in rat liver microsomes, isolated perfused rat livers, and rats with bile duct cannulas. In all three preparations, 4-desmethylgriseofulvin and 6-desmethylgriseofulvin were the major metabolites. The ratio of total 4-desmethylgriseofulvin to 6-desmethylgriseofulvin formed was 1.20, 0.89, and 1.01 in liver microsomes, isolated perfused livers, and rats with bile duct cannulas, respectively. After a 7-min incubation with liver microsomes, most (96%) of the griseofulvin remained unchanged. Only small amounts of 4-desmethylgriseofulvin (1.26%) of dose) and 6-desmethylgriseofulvin (1.05% of dose) were formed. In isolated perfused liver, most of the drug (59% of dose) was excreted into bile within 4 hr, primarily as 4-desmethylgriseofulvin (24% of dose) and 6-methylgriseofulvin (24% of dose). In animals with bile duct cannulas, 65% of the dose was excreted into bile and 18% of the dose into urine within 4 hours. In bile, 32% of the dose was excreted as 4-desmethylgriseofulvin and 20% of the dose as 6-desmethylgriseofulvin, whereas in urine the drug was excreated predominantly as 6-desmethylgriseofulvin (13% of dose) with only a small amount of 4-desmethylgriseofulvin (1% of dose), during the first 4 hr. These results show that there is good correlation in the metabolic fate of 14C-griseofulvin in the liver microsomes, isolated perfused liver, and rats with bile duct cannulas. In addition to the similar ratio of 4-desmethylgriseofulvin to 6-desmethylgriseofulvin, there is also an agreement in the extent of metabolism and biliary excretion in isolated perfused liver and in rats with bile duct cannulas, which suggests that the isolated perfused liver is an important technique for studying drug metabolism in animals.

Animals↗
PubMed2001

Genes of SHR rats protect spontaneously diabetic BB/OK rats from diabetes: lessons from congenic BB.SHR rat strains.

Diabetes in BB rats share many common features with human type 1 diabetes. One of them is the complex and polygenic nature of disease. Analysis of cross hybrids of diabetic BB/OK rats and rats of different diabetes-resistant strains has demonstrated that beside the MHC genes, Iddm1 and the lymphopenia, Iddm2, additional non-MHC genes are involved in diabetes development. To study the importance of the non-MHC genes, Iddm4 and Iddm3, two congenic BB.SHR rat strains were generated by recombining a segment of the SHR chromosome 6 (Iddm4; termed BB.6S; 15cM) or chromosome 18 (Iddm3; termed BB.18S; 24cM) into the BB/OK background by serial backcrossing and marker-aided selection. The characterization of both congenic strains demonstrates a drastic reduction of diabetes frequency in comparison to the BB/OK strain (86% vs 14% and 34%). It is supposed that diabetes protective genes of SHR must be located on both chromosomal segments and that these suppress the action of the essential and most important genes of diabetes development in the BB/OK rat, Iddm1, and Iddm2.

Animals↗
PubMed2006

Motion perception in rats (Rattus norvegicus sp.): deficits in albino Wistar rats compared to pigmented Long-Evans rats.

Motion perception was tested in pigmented Long-Evans and albino Wistar rats (Rattus norvegicus sp.) using moving random dot patterns. Pigmented as well as albino rats could distinguish a fully coherently moving pattern from dynamic noise. However, motion coherence thresholds were significantly lower in pigmented compared to albino rats (12% and 30% coherence, respectively). These results indicate that pigmented rats have well developed motion coherence perception, whereas albino rats are severely impaired but not motion blind.

Animals↗
PubMed2002

Chronic feeding of a nitric oxide synthase inhibitor induces postprandial hypertriglyceridemia in type 2 diabetic model rats, Otsuka Long-Evans Tokushima Fatty rats, but not in nondiabetic rats.

Postprandial hyperlipidemia is frequently associated with diabetes mellitus and considered to be an independent coronary risk factor. Nitric oxide (NO) is a key regulator of glucose uptake in skeletal muscle. The goal of this study was to examine the effects of chronic in vivo competitive antagonism of NO synthase (NOS) by the administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) on glucose and lipid metabolism in diabetic (Otsuka Long-Evans Tokushima Fatty [OLETF]) and nondiabetic rats. Chronic administration of L-NAME to rats induced reduced NO production and hypertension in both strains of rats. No detectable impairment of plasma levels of postprandial triglyceride (TG) or insulin sensitivity in nondiabetic rats was detected by chronic treatment of L-NAME, but significant impairment was observed in the cases of diabetic rats. These results suggest that diabetes, when associated with endothelial dysfunction, results in greater abnormalities in lipid, as well as glucose metabolism.

Animals↗
PubMed1995

A synthetic peptide corresponding to residues 645-653 in the carboxyl terminal cytoplasmic domain of the rat testicular follicle stimulating hormone receptor modulates G protein coupled-receptor signaling in rat testis membranes and in intact cultured rat Sertoli cells.

We examined the involvement of the carboxyl terminal cytoplasmic domain (residues 645-653) of the rat testicular FSH receptor in FSH signal transduction utilizing light membranes prepared from immature rat testes, intact cultured rat Sertoli cells, and a synthetic peptide approach. This region of the FSH receptor was selected because of its structural similarity to receptor-G protein contact sites identified in other G protein-coupled receptors. FSHR- (645-653) peptide amide promoted guanine nucleotide exchange in rat testis membranes, presumably via its interaction with membrane-associated G protein, but did not inhibit FSH binding to testis membrane receptors. When incubated with intact cultured Sertoli cells from immature rat testes, FSHR- (645-653) peptide amide consistently and significantly stimulated basal cAMP and estradiol biosynthesis. The peptide had no effect on forskolin stimulation of cAMP and estradiol, but inhibited FSH stimulation of each. FSH binding to receptor was unaffected by the peptide, these results suggest peptide interaction with receptor-associated G protein. The effects of FSHR- (645-653) peptide amide on FSH-stimulated estradiol biosynthesis were prevented by pretreating Sertoli cells with phenylarsine oxide, an inhibitor of FSH receptor internalization. These results suggest that peptide effects in intact Sertoli cells were related to peptide entry into the cell, presumably during receptor-mediated endocytosis of FSH, or by diffusion. Synthetic peptide amides not satisfying structural criteria for G protein coupling had no effect on either guanine nucleotide exchange or estradiol biosynthesis, even at concentrations significantly higher than used for FSHR- (645-653) peptide amide.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Effect of ethanol on hepatobiliary transport of cationic drugs. A study in the isolated perfused rat liver, rat hepatocytes and rat mitochondria.

The effect of ethanol on the hepatic uptake of various cationic drugs was studied in isolated perfused rat livers, isolated rat hepatocytes and isolated rat liver mitochondria. In isolated rat hepatocytes and in isolated perfused rat livers, the uptake of the model organic cation tri-n-butylmethylammonium was found to be markedly stimulated by ethanol in a concentration-dependent fashion. The uptake of tri-n-butylmethylammonium at 1 microM was increased to 120% and 137% at 0.5% (v/v, (= 87 mM)) and 1% (v/v. (= 174 mM)) ethanol, respectively. At 25 microM, tri-n-butylmethylammonium uptake was increased to 124% and 152% at 0.5% (v/v) and 1% (v/v) of ethanol, respectively. The uptake of the organic cations azidoprocainamide methoiodide, vecuronium, ORG 9426 and ORG 6368, the anionic compound taurocholate and the uncharged compound ouabain was not markedly increased at these ethanol concentrations. The mechanism of action of ethanol on the uptake of tri-n-butylmethylammonium was further studied. Competitive inhibitors for the type I organic cation uptake system, procainamide ethobromide and verapamil, almost completely blocked uptake of tri-n-butylmethylammonium (1 microM) in the presence of 1% (v/v) ethanol, indicating that carrier-mediated uptake is still involved and that additional passive diffusion is unlikely. Neither the plasma membrane potential nor the accumulation of the cation in mitochondria was altered after ethanol treatment, suggesting that potential driving forces for uptake and sequestration were not affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1997

Effects of rat galanin and galanin message associated peptide (GMAP) on rat growth hormone secretion and stimulating effect of gamma-aminobutyric acid on galanin release from rat hypothalamus.

Immunoreactive galanin and galanin message associated peptide (GMAP) were detectable in rat hypothalamus in the concentration of 563 +/- 23 and 14.3 +/- 3.1 fmol/hypothalamus, respectively. gamma-Aminobutyric acid (GABA) elicited a dose-related increase in galanin release from rat hypothalamic fragments, which was inhibited by picrotoxin, a GABA antagonist. Growth hormone (GH) secretion from rat anterior pituitary cells were stimulated by rat galanin, but not by GMAP. These findings suggest that hypothalamic galanin, but not GMAP, may play roles in GH secretion induced by GABAergic mechanisms in the rat.

Analysis of Variance↗
PubMed1990

Binding of aromatic amines to the rat hepatic Ah receptor in vitro and in vivo and to the 8S and 4S estrogen receptor of rat uterus and rat liver.

Studies on structurally related aromatic amines with different carcinogenic properties have shown that 2-acetylaminofluorene (2-AAF) and 2-acetylaminophenanthrene (AAP) inhibit the binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin to the Ah receptor in vitro. The apparent inhibitor constants (Ki) are 2.3 microM for 2-AAF and 2.7 microM for AAP. In contrast, 4-acetylaminofluorene, an isomer of 2-AAF, and trans-4-acetylaminostilbene do not bind to the rat hepatic cytosolic Ah receptor. Pretreating female Wistar rats with 2-AAF or AAP leads to the induction of the P-450 isoenzymes that are under the control of the Ah receptor. Ornithine decarboxylase activity is induced by all aromatic amines tested irrespective of their Ah receptor affinity. The aromatic amines used as model compounds do not inhibit the binding of 17-beta-estradiol to the 8S and 4S estrogen receptor of rat uterus or rat liver in a competition assay analyzed using sucrose density gradient centrifugation. On the other hand, the aromatic amines bind to varying extents to another estrogen-binding protein of rat liver whose function and identity is still unknown. Our study demonstrates that structurally related aromatic amines in their unmetabolized form interact differentially with a cellular target protein, the Ah receptor, in vitro as well as in vivo. However, a relationship between these effects and the postulated promoting properties of 2-AAF remains to be established.

Amines↗
PubMed1982

A comparison of plasminogen activators derived from rat plasma, primary rat hepatocytes and isolated perfused rat liver.

Of the two cell types it was possible to culture from the dissociated rat liver, hepatocytes and Kupffer cells, only the former were fibrinolytically active. Rat hepatocytes during the first 24 hr in culture secreted two plasminogen activators with molecular weights identical to those found in rat plasma, an 80,000-dalton form (PA-80) and a 45,000-dalton form (PA-45). Partially purified preparations of plasminogen activators from both sources were subjected to isoelectric focusing (IEF) to compare characteristics further. There were three distinct peaks of PA-45 in each preparation with isoelectric points of 7.1, 7.2 and 7.4; all electrophoretic forms had the same low affinity to fibrin. PA-80 from both sources displayed similar IEF profiles with forms ranging from pH values of 7 to 8, all with the same high affinity to fibrin. The major form of PA-80 in the plasma preparation had an isoelectric point of 7.9 whereas that in the hepatocyte preparation had an isoelectric point of 7.6. The isolated perfused rat liver was also shown to produce both PA-80 and PA-45 emphasizing the physiological relevance of the findings with hepatocytes. It is concluded that in the rat hepatocytes contribute to the plasma profile with regard to the plasminogen activator content.

Animals↗
PubMed1987

Comparative morphometric analysis of cochlear vessels in Wistar-Kyoto rats, spontaneously hypertensive rats, and aged spontaneously hypertensive rats.

Vessel density and the ratio of the tissue area to the vessel surface area were studied by morphometric analysis techniques in normal rats, spontaneously hypertensive rats (SHR), and aged spontaneously hypertensive rats (aged SHR). Horseradish peroxidase was injected intravenously and the animals were killed 10 minutes later. The temporal bones were harvested, fixed in glutaraldehyde, and decalcified in 10% ethylenediamine tetraacetic acid (EDTA). After 7 days of decalcification, the cochleas were dissected and incubated with a diaminobenzidine tetrahydrochloride solution. Sections with stained vessels were projected onto the digitizing plate with the help of the camera lucida. The computer was used to calculate tissue area, vessel length, and vessel surface area. A statistically significant increase (p less than 0.05) in both the tissue area to vessel length ratio and the tissue area to vessel surface area ratio was demonstrated in the SHR and the aged SHR groups when compared to the WKY in the stria vascularis. No statistically significant difference was found between the two SHR groups. These data show a decrease of the vessel density in the capillary beds of the stria vascularis in spontaneously hypertensive rats. No statistically significant difference was found in the diameters of the capillary among the three groups.

Animals↗
PubMed1977

[Comparative study of somatic and visual projections on the cerebral cortex of the normal adult rat, the rat enucleated at birth, and the young rat].

A comparative study of somatic and visual projections on the cerebral cortex of the adult of the normal rat or of the rat enucleated at birth, and of the young rat. This study was first designed to examine the developmental features of somate, sensory and visual projections to the rat cerebral cortex, together with their alteration as a consequence of early sensory deafferentation. We were led to a reevaluation of these projectins in the normal adult rat. This study specifically shows that topical projections exist, for both the somatic and the visual system. However, projections that are highly convergent in nature are present over most of the superolateral aspect of the cerebral cortex and we were unable to demonstrate any simple change resulting from early visual deafferentation.

Afferent Pathways↗
PubMed1987

Growth and development of rats artificially reared on rats' milk or rats' milk/milk-substitute combinations.

Rat pups were artificially reared (AR) from post-natal day 5 by intermittent gastric infusion. Mother-reared (MR) siblings served as controls. Fourteen measures of body and organ growth were taken at the end of each experiment. In Expt 1, two batches of pups were given rats' milk only, obtained by manual expression from anaesthetized dams. The first batch, reared to 12 d, grew less well than the MR group, probably because they received too little milk. However, relative to body-weight, organ weights were as great or greater than those of MR pups, except for heart weight. The second batch, given more milk and reared to 20 d, showed no deficits in organ or body-weights, but excesses in kidney, gastrocnemius muscle, stomach and caecum weights. There were no losses from 'bloat', a condition of gastrointestinal distention often encountered in artificial rearing with milk substitutes. Obtaining rats' milk is extremely labour-intensive and in Expt 2, more economical regimens were devised in which pups were started off on expressed rats' milk and then changed to a milk substitute resembling rats' milk in composition, either abruptly at 12 d or gradually between 8 and 17 d. Both regimens were successful, in that there were no losses from bloat and most measures of growth were at least as great as in the MR group. Only heart weight was lower in both AR groups and adrenal weight in the abruptly changed AR group. The weights of the stomach and caecum and the length of the small intestine were all high in both AR groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗
PubMed1993

Early renal disease in BHE/cdb rats is less in rats fed beef tallow than in rats fed menhaden oil.

The effects of feeding a 1% corn oil-9% menhaden oil or beef tallow diet on the early phase of diabetic nephropathy in BHE/cdb rats was studied. The diet groups were subdivided into rats with or without impaired glucose tolerance. Those fed menhaden oil had renal hypertrophy, mild albuminuria, decreased creatinine clearance, increased urea clearance, and more severe lesion scores than rats fed beef tallow. No differences in glomerular filtration rate, Na+, K+-ATPase activity, sorbitol dehydrogenase, or inositol 1, 4, 5-phosphate were observed. Beef tallow-fed rats had higher serum triglyceride levels and renal cholesterol levels. Renal and hepatic fatty acid profiles reflected the fatty acid profile of the dietary fat. These results suggest that beef tallow conferred a protective effect on the renal tissues of these diabetes-prone rats.

Albuminuria↗
PubMed1991

Study on rat-rat hybridoma technique and production of rat monoclonal antibodies against HIV and HBsAg.

The rat-rat hybridoma technique has some definite advantages in the three systems (mouse, rat or human system) currently utilized for monoclonal antibody production. The study on rat-rat hybridoma technique and its application to the productions of monoclonal antibodies against human immunodeficiency virus (HIV) and hepatitis B virus surface antigen (HBsAg) are described as examples in this paper.

Animals↗