The effects of physostigmine on the oxygen uptake in rat brain tissue.

Physostigmine in a dose of 0.1 mg/kg i.v. expressly stimulated the oxygen uptake in the rat cerebral cortex. This effect was blocked by propranolol and seems be mediated by catecholamines. Since atropine also antagonized the stimulant effect of physostigmine, it appears that the action of physostigmine is primarily cholinergic and that the adrenergic effect is a secondary phenomenon. The higher dose of physostigmine (0.4 mg/kg i.v.) caused a depression of rat brain oxygen uptake.     

The dopamine autoreceptor agonist B-HT 920 markedly stimulates sexual behavior in male rats

Summary B-HT 920, a selective agonist at dopamine (DA) autoreceptors, strongly increased the incidence of penile erections (PE) in male rats, an effect which was dose-related and antagonized by haloperidol. B-HT 920 at 100 and 200 g/kg i.p. significantly altered the copulatory pattern of sexually active male rats, reducing the number of mounts and intromissions as well as the latency to the first ejaculation, a stimulant effect which was confirmed in sluggish males at a dose of 100 g/kg.     

Alpha adrenergic control of growth hormone in adult male rats

Summary Intravenous injection of 0.1 mg/kg clonidine into rats under urethane anaesthesia induced a prompt and long-lasting release of growth hormone, estimated by radioimmunoassay (IRGH), which could be abolished by 0.2 mg/kg phentolamine given into the 3rd ventricle. Injection of 3 g/kg clonidine into the 3rd ventricle stimulated also the release of IRGH significantly. Intravenous administration of 0.32 mg/kg phenylephrine caused a small and transient release of IRGH only. These results provide evidence that central -adrenergic stimulation resulting in an increased GH secretion is one importantmechanism in the regulation of this hormone in the rat.     

Uptake of D-glucose anomers by rat retina

Summary Uptake ofd-glucose anomers by isolated rat retina was studied. After 3 min incubation at 37°C in the presence of or anomer (750 g/ml), a significantly greater uptake (1.32 mg/g wet tissue) of -anomer was observed compared with that of -d-glucose (1.11 mg/g wet tissue). This result and other data suggest that the carrier ford-glucose transport in the retina prefers the -anomer stereospecifically.Acknowledgment. The authors are grateful to Mr S. Suzuki for his technical assistance.     

Interaction of CDP-choline with synaptosomal transport of biogenic amines and their precursors in vitro and in vivo in the rat corpus striatum

Summary Added to a striatal synaptosomal homogenate of rat brain, CDP-choline 10^–4 M inhibits the uptake of norepinephrine (NE), dopamine (DA) and serotonin (5 HT) in a competitive fashion and enhances the uptake of tyrosine and tryptophan; administered to animals, CDP-choline (50 mg/kg/l h/i.v.) inhibits only the in vitro uptake of DA but enhances the uptake of precursors.This research was supported by CNRS grant (ERA No. 560) and Inserm grant (FRA 5).     

Involvement of H1 receptors in the central antinociceptive effect of histamine: Pharmacological dissection by electrophysiological analysis

Intracerebroventricular (i.c.v.) administration of histamine (HA, 0.025–0.1 M/rat) to arthritic rats induces a dose-related inhibition of the neuronal thalamic firing evoked by peripheral noxious stimuli. To characterize the type(s) of HA receptors involved in this depressing activity of the amine we used electrophysiological techniques to examine the effects of i.c.v. administration of H₁ and H₂ agonists and antagonists on the spontaneous and evoked nociceptive firing of the thalamic neurons in rats rendered arthritic by Freund's adjuvant. The H₁ agonist 2-pyridylethylamine (0.4–1.0 M/rat, i.c.v) displayed a dose-dependent antinociceptive effect very similar to that of HA, while the H₂ agonist dimaprit (0.05–0.2 M/rat, i.c.v.) did not modify thalamic firing. Neither mepyramine (H₁ antagonist, 0.1 M/rat, i.c.v.) nor zolantidine (H₂ antagonist, 0.01 M/rat, i.c.v.) modified the evoked firing of rat thalamic neurons. When administered before HA (0.1 M/rat, i.c.v.) mepyramine but not zolantidine was able to inhibit the antinociceptive effect of HA. On the basis of the present electrophysiological results, we suggest that a specific interaction of histamine with H₁ receptors may be important for its antinociceptive effect on afferent peripheral inputs to the thalamus.     

The effect of camphor on mitochondrial respiration

Summary Camphor at <8 moles/mg protein reduced the rate of oxygen consumption by rat liver mitochondria. The effect occurs only with NAD⁺-linked substrates. Succinate linked respiration was inhibited but this appears to be caused by some conversion of succinate to malate. At higher levels, camphor increases oxygen consumption with succinate substrate, by uncoupling at site II.Acknowledgment. D.F.G.-C. is grateful to the New Zealand Cancer Society (Wellington Branch), for financial support. We thank Mrs E. Dye for technical assistance and Dr W. Jordan for valuable discussions.     

Experimental catalepsy: Influences of cholinergic transmission in restraint-induced catalepsy

Summary Possible cholinergic mechanisms in experimental catalepsy were evaluated by using the pinch-induced model in mice. In control, saline-injected mice, the median number of attempts needed to achieve a criterion level of catalepsy was 6. All 3 dose levels of physostigmine reduced this median to about 2 trials; neostigmine did not significantly reduce the number of trials. Opposite effects were obtained with atropine, with which all 3 doses tested increased the number of trials needed to cause catalepsy, and at the higher doses (5 and 10 mg/kg) most of the mice (80%) became insusceptible; atropine methyl bromide had no such effects. Thus, this kind of catalepsy may be mediated by cholinergic mechanisms that are central and not peripheral.     

Interaction of CDP-choline with synaptosomal transport of biogenic amines and their precursors in vitro and in vivo in the rat corpus striatum.

Added to a striatal synaptosomal homogenate of rat brain, CDP-choline 10(-4) M inhibits the uptake of norepinephrine (NE), dopamine (DA) and serotonin (5 HT) in a competitive fashion and enhances the uptake of tyrosine and tryptophan; administered to animals, CDP-choline (50 mg/kg/l h/i.v.) inhibits only the in vitro uptake of DA but enhances the uptake of precursors.     

Activité antifibrillante chez l'animal d'un nouveau dérivé de la phényl-éthylamine

Summary A new synthetic phenyl-ethyl-amine derivative, the 2-[N- (3, 4-methylen-dioxyphenylethyl)-methylaminomethyl]-tetrahydrofuran, No. 11 081, exhibits a strong protective effect against cardiac fibrillation and arrhythmias produced by various experimental methods: against fibrillation due to aconitine 3 × 10^–8 on the isolated cat's heart, it is active in a concentration of 10^–6–2 × 10^–6. Against cardiac arrhythmias produced in the cat by adrenaline + CHCl₃ or cyclopropane, it shows a protective effect by 5–10 mg/kg i.v. and even perorally by 50 mg/kg. In these tests, the antifibrillatory activity of the new compound seems to be roughly the same as that of -fagarine, and higher than that of procaine.

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9^e communication sur les dérivés des alcoylène-imines; 8^e communication, cf. Exper.10, 261 (1954).     

Influence of repeated prazosin administration on cardiovascular responses in rats and rabbits

Prazosin was injected i.v. at a dose of 50 g/kg every 2 h for 8 h in conscious rats. Its hypotensive action significantly declined. A similar effect was also observed in rabbits pretreated with prazosin (40 g/kg, i.v.) every 1 h for 4 h. In prazosin-treated rabbits, the total peripheral resistance became less responsive to phentolamine stimulation. Repeated prazosin administration abolished its ability to block receptors in a model of anococcygue muscle contraction after noradrenaline (NA) stimulation. The -adrenoceptors in anococcygue muscle exhibited lower pD₂ to NA and lower pA₂ to prazosin in prazosin-treated rats. The results demonstrate that repeated prazosin administration reduces the effectiveness of -adrenoceptors blockers.     

A centrally induced vasodepressor response after intravenous administration of whole venom ofNaja mossambica pallida in cats

Summary Naja mossambica pallida venom administered i.v. (300 /kg) produces an initial brief fall in blood pressure, due to a direct myocardial depressant effect, and a sustained fall due to central depressant effect.This study was supported by University of Nairobi research grants (670–376). We also thank Mr E. Njogu for photographic assistance.     

The COMT inhibitor tolcapone potentiates the anticataleptic effect of Madopar in MPP+-lesioned mice

Orally administered Madopar (levodopa/benserazide 41) dose-dependently antagonized haloperidol-induced (1 mg/kg s.c.) catalepsy in MPP⁺-lesioned mice. Pretreatment with a new selective catechol-O-methyltransferase (COMT) inhibitor, tolcapone (30 mg/kg p.o.), slightly potentiated the antagonistic effect of Madopar (15 mg/kg p.o.) on haloperidol-induced catalepsy. The ability of tolcapone to increase the Madopar effect was significantly attenuated by high doses of 3-O-methyldopa (3-OMD) (800 mg/kg i.p.). This might suggest a competitive blockade of the active transport of levodopa through the blood-brain barrier. In conclusion, the inhibitory effect of tolcapone on the O-methylation of levodopa to 3-OMD by COMT is largely due to improved levodopa and dopamine availability in the brain, and to the reduced formation of 3-OMD.     

Effect of praseodymium on drug metabolism in rat liver smooth and rough endoplasmic reticulum

Summary A small i.v. dose (3 mg/kg) of a light lanthanon, praseodymium, impairs the drug metabolizing capacity of both the smooth and rough fractions of rat liver endoplasmic reticulum. This decrease in the activity of drug metabolizing enzymes and in the amount of cytochromes P-450 and b₅ is more pronounced in the rough endoplasmic reticulum fraction.     

Prostaglandin-induced serotonin release

Zusammenfassung Bei Ratten wurde die Gesamtmenge von Serotonin in der Fundus- und Atriumschleimhaut sowie im mittleren Jejunum bestimmt. Prostaglandin E₁ (200 g/kg, s.c. oder i.v.) reduzierte den Serotoninspiegel weder in den Kontrolltieren noch in mitp-Chlorophenylalanin (150 oder 300 mg/kg) oder mit Reserpin (5 mg/kg) vorbehandelten Tieren.     

Inhibition of food intake in the rat by cyproheptadine

Summary In a model of conditioned feeding behavior, oral administration of cyproheptadine (1–100 mg/kg), 30 min before presentation of food, produced a dose-dependent reduction of food intake in the rat (ED₅₀17 mg/kg during the 1st h of testing). This anorexic effect persisted for at least 24 h. These results provide further evidence that under certain conditions cyproheptadine, which is used as an orectic agent in man, can produce anorexia.     

Rat mammary cancer inhibition by a prolactin suppressor, 2-bromo-α-ergokryptine (CB 154)

Zusammenfassung 2-Br--Ergokryptin (=CB 154) wurde täglich während 80–100 Tagen, beginnend mit der Carcinogenapplikation, DMBA - (5 mg i.v.)-behandelten weiblichen Ratten in der Dosis 6 mg/kg i.p. verabreicht. CB 154 bewirkte ein verzögertes Erscheinen und ein langsameres Wachsen der Mamma-Tumoren sowie eine verminderte Todesrate der carcinogenbehandelten Ratten.     

Amylin given by central or peripheral routes decreases gastric emptying and intestinal transit in the rat

The effect of rat amylin on gastric emptying and intestinal transit in the rat was examined. Amylin administered intracerebroventricularly (1, 2, 2.5 or 4 g/rat) produced the maximal decrease in gastric emptying and intestinal transit at the dose of 2.5 g/rat. Higher doses produced a lower effect. Peripheral administration (25, 50 or 100 g/kg) produced dose-dependent effects. Pre-treatment with neostigmine blocked the effect of amylin when it was centrally injected, while the effect of amylin given peripherally was partially reduced. Pre-treatment with domperidone decreased the inhibitory effect of peripherally injected amylin, but no effect was observed when the peptide was centrally injected.     

Dopamine and cerebral cortical blood flow in the rat

Summary Dopamine topically applied to the cerebral cortex (1–20 g/ml) or administered i.v. (0.5–64 g/kg/min) has no effects on cerebral cortical blood flow in the rat.     

Tumor necrosis factor-α inhibits collagen synthesis in human and rat granulation tissue fibroblasts

The purpose of the study was to examine the effects of tumor necrosis factor- (TNF-) on collagen gene expression in rat and human granulation tissue fibroblast cultures. The cells were exposed to 0.1, 1, 10, or 100 ng/ml of TNF-, and the rate of collagen synthesis was measured as synthesis of protein-bound³H-hydroxyproline. Total cellular RNA was isolated from fibroblasts, and measurements of specific cellular RNAs from fibroblasts were performed by Northern blot hybridizations using³²P-labeled cDNA probes. In cultures of rat granulation tissue fibroblasts TNF- decreased³H-hydroxyproline production to about 75% of that in controls and it also decreased pro1(I) and pro1(III) collagen mRNA levels, maximally to 33% and 23% of the control levels, respectively. In cultures of human granulation tissue fibroblasts a similar inhibiting effect in the production of collagen was seen. TNF- decreased the production of³H-hydroxyproline to 56% of the control value with a dose of 100 ng/ml also having an inhibiting effect on pro1(I) collagen mRNA levels of up to 43% of the control level. However, no effect was seen on pro1(III) collagen mRNA levels.