Modification of the action of pentagastrin on acid secretion by botulinum toxin

Summary I.v. botulinum toxin after 60–90 min abolished the dose-response relationship between pentagastrin and gastric acid secretion in anesthetized rats and guinea-pigs. The toxin reduced but did not abolish the acid stimulatory effect of histamine. As expected, the acid response to vagal stimulation was abolished and that to methacholine in rats was unaltered by the toxin.Acknowledgment. We are grateful to the generosity of Dr Edward J. Schantz, Food Research Institute, University of Wisconsin, for the botulinum toxin used. — This research was supported by NIH grant 1 RO1 AM 17125, The Secretion of Pepsin.     

Zinc antagonizes the effect of botulinum type A toxin at the mouse neuromuscular junction

Zn2+ (10-100 microM) elevated the frequency of miniature end-plate potentials (MEPPs) in the mouse diaphragm. The effect did not depend on external Ca2+. Botulinum type A toxin (BTXA, 50 ng/ml) abolished MEPPs almost completely within 30 min. Zn2+ (100 microM) restored MEPPs and increased their frequency after they had been abolished by BTXA in Ca2+ -free solutions. The antagonistic effect of Zn2+ in the Ca2+ -free solution was reduced by exposing the diaphragm to the toxin in the Ca2+ -free solutions containing high K+. Thus, the action of BTXA is probably enhanced by depolarization of the motor nerve terminals.     

Effects of L-aspartic acid,L-asparagine and/or L-asparaginase on forced swimming-induced immobility,analgesia, and decrease in rectal temperature in rats

Summary The effect of L-aspartic acid, L-asparagine and/or L-asparaginase were compared with those of imipramine on immobility, number of defecations, increase of nociceptive threshold, and hypothermia, induced by forced swimming in rats. L-Aspartic acid was found to be as effective as imipramine in reducing the effects of forced swimming, presumable by normalizing the decreased level of endogenous L-aspartic acid, due to the inhibition of L-asparaginase activity and/or by stimulated the inhibited enzyme. The other treatments antagonized the immobility, but not the increased number of defecations. All compounds abolished the elevation of nociceptive threshold and hypothermia.     

Erzeugung von Rigor der Rattenxtremitäten durch Hemmung der Glyzin-Synthese

Summary Inhibition of glycine synthesis by aminopterine, an antagonist of pteroilglutaminic acid, causes rigidity of hind limbs in rats. This rigidity can be abolished by the injection of glycine.     

Inhibition by the enterotoxin of Vibrio cholerase of meiosis reinitiation of the Xenopus laevis oocyte induced in vitro by progesterone]

Progesterone reinitiates in vitro meiosis in Xenopus laevis oocytes. This action of the hormone can be abolished by the exotoxin of vibrio cholerae. The concentration of toxin which inhibits 50% of the progesterone (10 muM) action in about 2.5 pM. Binding experiments using 125I labelled toxin demonstrated the existence of high affinity binding sites (KD approximately 0.2 nM) located probably on the surface of the oocytes.     

Different neuropathological effects of intrahippocampal injections of kainic acid and tetanus toxin

Behavioral and neuroanatomical effects of hippocampal injections of kainic acid (KA) and tetanus toxin (TT) were investigated in rats. Injections of KA resulted in both local and distant neuroanatomical damage, but not in clear signs of epilepsy; injections of TT on the other hand were followed (in some of the rats) by prolonged seizure attacks, but not by neuronal damage. Based on these results it is suggested that the widespread neuronal damage following KA lesions cannot be primarily attributed to orthodromic activation of epileptic discharges. Instead, specific properties of KA and their interactions with certain transmitters may provoke widespread neuroanatomical damage.     

Inhibition by tetanus and botulinum A toxin of the release of [3H]noradrenaline and [3H]GABA from rat brain homogenate

Rat brain homogenate was preloaded with [3H]noradrenaline or [3H]GABA and stimulated with high K+. Tetanus toxin and botulinum A neurotoxin partially prevent the evoked [3H]noradrenaline release in the same range of toxin concentrations starting below 10(-10) M. In contrast, release of gamma-amino butyric acid (GABA) is much more sensitive to tetanus than to botulinum A toxin.     

Zinc antagonizes the effect of botulinum type A toxin at the mouse neuromuscular junction

Summary Zn²⁺ (10–100 M) elevated the frequency of miniature end-plate potentials (MEPPs) in the mouse diaphragm. The effect did not depend on external Ca²⁺. Botulinum type A toxin (BTX_A, 50 ng/ml) abolished MEPPs almost completely within 30 min. Zn²⁺ (100 M) restored MEPPs and increased their frequency after they had been abolished by BTX_A in Ca²⁺-free solutions. The antagonistic effect of Zn²⁺ in the Ca²⁺-free solution was reduced by exposing the diaphragm to the toxin in the Ca²⁺-free solutions containing high K⁺. Thus, the action of BTX_A is probably enhanced by depolarization of the motor nerve terminals.     

Effect of mycotoxin (T-2 toxin) on catecholamine and Na+, K+-ATPase levels in rat epididymis

The effect of mycotoxin (T-2 toxin) on catecholamines and Na+, K+-ATPase activities in rat epididymis has been evaluated. Dopamine and norepinephrine levels were significantly elevated in the caput and corpus regions whereas their levels remained unchanged in the caudal part of the epididymis. Na+, K+-ATPase activity was significantly increased in all the three regions of rat epididymis as a result of the toxin treatment. These changes may suggest an adverse effect on epididymal functions in rats.     

Lack of pressor effect of dopamine in the pentobarbital-anesthetized rat

The blood pressure and heart rate responses to intravenous dopamine infusion at 2.5, 5.0 and 10.0 micrograms.min-1 X 100 g-1 were studied in conscious and pentobarbital-anesthetized Sprague-Dawley rats. In the conscious rats, dopamine caused a significant dose-related increase in the mean arterial blood pressure which was abolished in the anesthetized rats. The heart rate increased significantly only at the highest dose infused. The responses to equipressor doses of noradrenaline (40 ng.min-1 X 100 g-1) and phenylephrine (1.0 micrograms.min-1 X 100 g-1) were also suppressed in the anesthetized rats. The results suggest that pentobarbital anesthesia depresses the blood pressure response to dopamine infusion in the rat through a depression of activation of alpha-adrenoceptors.     

Effect of mycotoxin (T-2 toxin) on catecholamine and Na+, K+-ATPase levels in rat epididymis

Summary The effect of mycotoxin (T-2 toxin) on catecholamines and Na⁺, K⁺-ATPase activities in rat epididymis has been evaluated. Dopamine and norepinephrine levels were significantly elevated in the caput and corpus regions whereas their levels remained unchanged in the caudal part of the epididymis. Na⁺, K⁺-ATPase activity was significantly increased in all the three regions of rat epididymis as a result of the toxin treatment. These changes may suggest an adverse effect on epididymal functions in rats.     

Alpha 1-adrenergic stimulation of ketogenesis and fatty acid oxidation is associated with inhibition of lipogenesis in rat hepatocytes

The effect of norepinephrine on fatty acid synthesis (3H2O incorporation into fatty acids), on fatty acid oxidation to CO2 and on ketogenesis was studied in isolated hepatocytes of fed rats. After incubation with norepinephrine (50 microM), lipogenesis was lower (5.7 +/- 1.1 nmoles 3H2O incorporated into fatty acids/mg dry weight/30 min) than in controls (7.5 +/- 1.7; n = 6, p less than 0.02). In contrast, (1-14C) palmitate conversion into total ketone bodies was increased to 10.9 +/- 1.8 nmoles/mg/30 min with norepinephrine, vs 8.5 +/- 1.6 in controls (p less than 0.05), and more (1-14C) palmitate was converted to 14CO2 with norepinephrine than in controls (1.48 +/- 0.10 nmoles/mg/30 min vs 1.06 +/- 0.11, p less than 0.05). The inhibitory effect of norepinephrine on lipogenesis was abolished by addition of the alpha 1-receptor blocker prazosin, but not by alpha 2 or beta-blockers. The results demonstrate that the ketogenic effect of norepinephrine is coupled with an inhibitory effect on lipogenesis which may be explained by diminished activity of acetyl-CoA carboxylase, diminished formation of malonyl-CoA and decreased activity of carnitine palmitoyl transferase I.     

Effect of splanchnectomy and vagotomy on the pepsinogen response to intragastric acid

Summary Perfusion of the stomach in the anaesthetized rat with saline acidified to pH 2.5 with hydrochloric acid induced a small but significant release of pepsinogen into the perfusate. This stumulus to secretion was unaffected by splanchnectomy but was abolished by vagotomy. It is concluded that to a modest degree acid secretion in the rat may stimulate pepsinogen secretion by a vagal pathway.     

Inhibition by tetanus and botulinum A toxin of the release of [3H]noradrenaline and [3H]GABA from rat brain homogenate

Summary Rat brain homogenate was preloaded with [³H]noradrenaline or [³H]GABA and stimulated with high K⁺. Tetanus toxin and botulinum A neurotoxin partially prevent the evoked [³H]noradrenaline release in the same range of toxin concentrations starting below 10^–10M. In contrast, release of -amino butyric acid (GABA) is much more sensitive to tetanus than to botulinum A toxin.     

Aging alters resynchronization of the circadian system in rats after a shift of the light-dark cycle

Four days following an 8-h advance of the light-dark cycle, the circadian rhythms in the pineal N-acetyltransferase activity and melatonin content reappeared in 7-week-old rats, but were still abolished in 24-month-old animals.     

Aging alters resynchronization of the circadian system in rats after a shift of the light-dark cycle

Summary Four days following an 8-h advance of the light-dark cycle, the circadian rhythms in the pineal N-acetyltransferase activity and melatonin content reappeared in 7-week-old rats, but were still abolished in 24-month-old animals.     

Reduction in dietary vitamin E prevents onset of hypertension in developing spontaneously hypertensive rats

Summary Reduction in dietary vitamin E intake in developing spontaneously hypertensive rats abolished the onset of hypertension which is normally evident by 3 months of age.Supported by a grant No. 4-6 to C.P.-A. from the Canadian Ontario Heart Foundation.     

Bilateral lesions of suprachiasmatic nucleus eliminate circadian rhythms of oxygen consumption and the respiratory quotient in rats

Bilateral lesions of the suprachiasmatic nucleus of the hypothalamus of rats abolished circadian rhythms of oxygen consumption and of the respiratory quotient (RQ). The RQ remained constant at a level intermediate between the maximum (about 1.0) and minimum (about 0.9) values in control animals.     

Bilateral lesions of suprachiasmatic nucleus eliminate circadian rhythms of oxygen consumption and the respiratory quotient in rats

Summary Bilateral lesions of the suprachiasmatic nucleus of the hypothalamus of rats abolished circadian rhythms of oxygen consumption and of the respiratory quotient (RQ). The RQ remained constant at a level intermediate between the maximum (about 1.0) and minimum (about 0.9) values in control animals.     

Acute cold exposure increases the glucagon sensitivity of thermogenic metabolism in the rat

Administration of glucagon to rats at 25 degrees C had no effect upon their VO2, while administration of noradrenaline or noradrenaline plus glucagon raised the VO2. At 5 degrees C, noradrenaline had no effect upon the cold-enhanced VO2, while glucagon caused a rise of 13.7%, implying increased glucagon sensitivity at 5 degrees C. The glucagon-induced enhancement of VO2 was abolished by concurrent administration of noradrenaline.