[The depression of hepatic drug-metabolizing enzyme activity in rats with carrageenan-induced inflammation. II. The effect on the status of plasma antipyrine concentration in rats].

The variation of hepatic drug-metabolism was investigated in male Wistar rats bearing hind paw edema induced by carrageenan (1%, 0.1 ml, s.c.

Different effects of peptidase inhibitors on dermorphin- and on [D-Arg2]dermorphin-induced antinociceptive activity.

The antinociceptive effects produced by the intracerebroventricular (i.c.v.

Concomitant increase in putrescine incorporation with transferrin uptake into rat reticulocytes.

Concomitant increase in putrescine incorporation with transferrin uptake into rat reticulocytes was found. [14C]Putrescine incorporation occurred in the presence of transferrin at 37 degrees C. The subcellular distribution of incorporated [14C]putrescine showed that the incorporation in the plasma membrane time dependently increased.

Augmentation of host resistance to Candida albicans infection in ascites tumor-bearing mice.

We found that the number of peripheral blood polymorphonuclear leukocytes (PMN) dramatically increased in both sarcoma 180 (S-180) and MM-46 mammary carcinoma (MM-46) ascites tumor-bearing mice, and mice required a remarkable resistance to Candida albicans infection via intravenous route. When the resistance was determined by number of cells of C. albicans in the kidney, a significant decrease in the number of fungal cells was observed in the kidneys of infected ascites tumor-bearing mice.

Chronic clonidine treatment and its termination: effects on penile erection and ejaculation in the dog.

The effects of chronic administration (4 weeks) of the alpha-2 adrenoceptor agonist clonidine (CL) and its termination on penile erection and ejaculation were investigated in male dogs. Penile erection and ejaculation were elicited by manual penile stimulation (for 5 min). CL (10 micrograms/kg/hr, s.

The optical resolution of racemic chlorpheniramine and its stereoselective pharmacokinetics in rat plasma.

An ovomucoid-conjugated column has been developed for the chiral stationary-phase liquid chromatographic resolution of racemic chlorpheniramine with a quantitation limit of 0.05 microgram mL-1. The assay was used to study the stereoselective kinetics of chlorpheniramine enantiomers in rats.

Induction of platelet-activating factor in mice by intravenous administration of a neutral fraction of bakers' yeast mannan.

A neutral subfraction of mannan of bakers' yeast (WNM) was found to show a lethal effect in mice when administered intravenously. Symptoms caused by intravenous (i.v.

Internalization model using rat liver plasma membrane for receptor-mediated endocytosis of epidermal growth factor.

We have demonstrated the internalization of epidermal growth factor (EGF) using membrane isolated from rat liver. The isolated membrane exhibited a saturation curve of the binding of 125I-EGF. Furthermore, competition between the binding of 125I-EGF and unlabeled EGF to the isolated membrane was observed.

A time-dependent inactivation of aromatase by 19-oxygenated androst-4-ene-3,6,17-triones.

19-Hydroxyandrost-4-ene-3,6,17-trione (19-OHAT), its 19-oxo derivative (19-oxo AT) and 4 beta, 5 beta-epoxyandrostane-3,6,17-trione (5) were synthesized as possible intermediates involved in a mechanism-based inactivation of aromatase caused by androst-4-ene-3,6,17-trione (AT). These compounds, inhibited the enzyme in a competitive manner with Ki's of 0.61, 7.

Structural study on a phosphorylated mannotetraose obtained from the phosphomannan of Candida albicans NIH B-792 strain by acetolysis.

A mixture of phosphorylated manno-oligosaccharides was isolated from the acid-stable domain of phosphomannan of Candida albicans NIH B-792 strain (serotype B) by acetolysis and was fractionated on a column of Bio-Gel P-2 equilibrated with 50 mM pyridine-CH3COOH buffer, pH 5.0. A monophosphorylated mannotetraose was isolated as the major constituent.

[D-Ala2]deltorphin II analogs with high affinity and selectivity for delta-opioid receptor.

Nine [D-Ala2]deltorphin II (DL-II:Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2) analogs having various aliphatic amino acids at positions 5 and 6 were synthesized to gain more information about the role of hydrophobic Val5,6 residues for the delta-opioid receptor selectivity. Binding assays of analogs replaced by Ala demonstrated the importance of hydrophobic Val5,6 residues in DL-II for delta-affinity and selectivity, and especially critical importance of Val5 residue for higher delta-selectivity. By enhancing the hydrophobicity of residues at positions 5 and 6, we have developed analogs with very high delta-affinity and selectivity over those of DL-II, e.

Interaction of doxapram and pentobarbital in mice.

We found a statistically significant increase in duration of pentobarbital-induced narcosis in doxapram-treated mice. The influence of doxapram (a respiratory stimulant) pretreatment on pentobarbital metabolism in mice was assessed by measurements of sleeping times, hypothermia, LD50 values, hepatic microsomal metabolism and relative plasma and brain levels of pentobarbital. When doxapram was given intraperitoneally 60 min.

Differential effects of substance P analogs on neurokinin 1 receptor agonists in the mouse spinal cord.

Effects of five substance P (SP) analogs on the licking, biting and scratching response induced by neurokinin (NK) 1 receptor agonists such as SP, physalaemin and (p-Glu6,Pro9)-SP (6-11) (septide) were studied after intrathecal injections in mice. Septide brought about a SP-like behavioral response, and was approximately 25 times more potent than the D-Pro9 analog, D-septide. When administered simultaneously with NK-1 receptor agonists, a putative SP antagonist, spantide inhibited SP-, physalaemin- and septide-induced behavioral response in a dose-dependent manner with ED50 values of 1.

Studies on analgesic oligopeptides. VII. Solid phase synthesis and biological properties of Tyr-D-Arg-Phe-beta Ala-NH2 and its fluorinated aromatic amino acid derivatives.

Tyr-D-Arg-Phe-beta Ala-NH2 (I) and its six fluorinated analogs were synthesized. Their opioid receptor binding properties were examined in vitro and their analgesic activity in vivo using the mouse writhing test. It was found that I was one of the most selective and potent mu-receptor agonists reported to date.

Synthesis and biochemical studies of 16- or 19-substituted androst-4-enes as aromatase inhibitors.

Androst-4-en-17-one derivatives [19-acetoxide 4, 16-bromides 14 and 15, 19,19-difluoride 18, and (19R,S)-19-acetylenic alcohol 25] and androst-4-en-17 beta-ol derivatives 3, 5, 10, 12, and 19 were synthesized and tested for their ability to inhibit aromatase in human placental microsomes. All the 17-oxo steroids, except compound 25 and 17,19-diol 3 of this series, were effective competitive inhibitors with apparent Ki's ranging from 170 to 455 nM. 19,19-Difluoro steroid 18 and 19-acetylenic alcohol 25, a weak competitive inhibitor (Ki = 7.

Modulation of epidermal growth factor binding to receptor by isoproterenol and cholera toxin in primary cultured hepatocytes.

The treatment of rat hepatocytes with isoproterenol induced the increase in the affinity of high affinity binding sites and the decrease in the number of low affinity binding sites of epidermal growth factor (EGF). Similar results were obtained from the pretreatment of hepatocytes with cholera toxin. These results suggest that adenylate cyclase affects the affinity and number of EGF-receptor in hepatocytes.

Effects of d- and dl-chlorpheniramine on serotonin and 5-hydroxyindoleacetic acid levels in the regional parts of rat brain.

The purpose of this study was to further investigate the effects of chlorpheniramine (d- and dl-forms) on the levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the regional parts of rat brain. After the intravenous administration of each form of chlorpheniramine, the 5-HT and 5-HIAA levels were measured by HPLC system. Each form of chlorpheniramine is effective in reducing 5-HIAA, but not 5-HT levels in most of the regional brain of rats.

Structural determination of D-mannans of pathogenic yeasts Candida stellatoidea type I strains: TIMM 0310 and ATCC 11006 compared to IFO 1397.

The structures of the cell-wall D-mannans of pathogenic yeasts of Candida stellatoidea Type I strains, IFO 1397, TIMM 0310, and ATCC 11006, were investigated by mild acid and, alkaline hydrolysis, by digestion with the Arthrobacter GJM-1 strain exo-alpha-D-mannosidase, and by acetolysis. The modified D-mannans and their degradation products were studied by 1H- and 13C-n.m.

[Modulation of anthracycline resistance by reserpine in P388 leukemia cells].

The activity of reserpine and a possible mechanism by which it reverses the resistance to both doxorubicin and pirarubicin in doxorubicin-resistant P388 leukemia (P388/DOX) cells were examined in vitro. During 48 hr drug-exposure, the sensitivity of doxorubicin and pirarubicin were potentiated markedly when reserpine was present at the concentration of 1 microgram/ml, which is not toxic to P388 leukemia (P388/S) cells. However, reserpine had little effect on the cytotoxicity of doxorubicin and pirarubicin in the sensitive parent cell.

Effect of sodium chloride on pirarubicin induced cell killing in P388 mouse leukemia cells.

The effect of sodium chloride on the cytotoxicity of 4'-O-tetrahydropyranyldoxorubicin (pirarubicin), a novel anthracycline derivative, was investigated on P388 mouse leukemia cells in vitro. The modifications in efficiency of uptake and killing action of pirarubicin were found to be dependent on the ionic strength of the medium. The relationship between intracellular drug accumulation into cells and cell killing was pointed out.

Changes in ingestive behavior induced by intracranial injection of spermine.

Effect of intracranial injection of spermine on feeding and drinking behavior was studied in rats. A significant and long-term suppression of feeding and drinking behavior appeared when 30 nmol/hemisphere of spermine was bilaterally injected into the lateral hypothalamic area, substantia nigra or ventral noradrenergic bundle. Micro-injected spermine into the medial amygdaloid nucleus produced a weak and short-time but significant suppression of ingestive behavior.

Exacerbation of doxorubicin toxicity by chlorpromazine in male ddY mice.

We examined whether chlorpromazine (CPZ) modulates the lethality of doxorubicin (DOX, 12 mg/kg, i.p.) in mice treated with CPZ (6 mg/kg, i.

Doxapram inhibits the in vitro oxidation of hexobarbital.

The effect of doxapram on the mouse liver microsomal hexobarbital metabolism in vitro was studied. Doxapram inhibited hexobarbital oxidase in a competitive manner, with inhibition constants between 2 and 10 mM. Doxapram induced a reverse type I spectral change with a spectral dissociation constant of about 0.