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The effects of levamisole on rat tracheal isolated rings
FACILITATION AND INHIBITION OF MUSCLE FUNCTION BY DIAZEPAM J. Khodabaks, H. van Wilgenburg and R.S. Leeuwin Department of Pharmacology, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. This study is an attempt to evaluate the biphasic effects of diazepam on muscle function. Phrenic nerve-diaphragm preparations from rats (180 g), killed by neck blow, were fixed in organ vessels containing Krebs-Ringer solution (37°C, pH 7.4, 5% CO 2 in 02). Stimulation fi'equencies were 0.1 Hz (5 rain) and 10 to 50 Hz (3 set). Both indirect (0.2 msec width) or direct (2.0 msec width) pulses were applied. Diazepam (3x10 -6 to 3x10 -4 M) in propylene glycol was added to the bath non-cumulatively; no6 for each concentration. Effects were expressed as percentage area under the curve of control. Estimated Emax at each frequency was obtained using Lineweaver-Burk plotting. Potentiation of the tetanic contractions correlated well (analysis o f variance P<0.05) with concentrations at the lower levels between l0 and 30 Hz (indirect stimulation) and 10 and 40 Hz (direct stimulation). At relatively high concentrations (3x10 -4 M) tetanic contractions were inhibited. The highest estimated Emax after indirect stimulation was found at 10 -4 M after 20 Hz, i.e. 582.4+14.6, and 436.5_+31.6 after 30 Hz at direct stimulation. The respective experimentally measured Emax' were 323.2_+40.6 and 358.8_+51.1. In conclusion, diazepam produces concentration- and frequency-dependent facilitation of m u s c l e function. The fact that after indirect stimulation the estimated Emax is significantly higher than the experimentally measured value may be attributed to inhibition of contractions at higher concentrations.
A L T E R A T E D MUSCLE ENERGY METABOLISM IN PATIENTS WITH CHRONIC RENAL FAILURE. O. Pastoris*, P. Foppa*, M. Catapano*, R. Aquilani§, P.
THE EFFECTS OF LEVAMISOLE ON RAT T R A C H E A L ISOLATED RINGS M.. Costulaanu, Et Teelarlu, C. Filip, A.Negru and Me N e c h i f o r Department of Pharmacology, University of Medloine and Pharmacy, University Street 16 R0-6600, Iasi, Romania
EFFECTS OF PROPOFOL ON SYMPHATETIC NEUROTRANSMISSION IN THE ISOLATED RAT VAS DEFERENS T. Kaya_, Y. Sarioglu, T. Utkarg C. Mimaroglu and K. Yildirim Cumhuriyet University, Faculty of Medicine, Department of Pharmacology, 58140, Sivas, Turkey.
L e v e m i s o l o , a widely used antiholmintio drug,has been shown to restore cutaneousdelayed h y p e r s e n s i t i v i t y in anerglc patients and t o a m p l i f y t h e a c t i v a t i o n of T lymphocytes by in vitro mltogans (Takl st al.,I-
mmtmopharmacol.Immunotoxicol.,1994,16,129), Levamisole can increase the cGMP levels in inflammatory ceXls (Roch-Arveiller et el., Agents Actlons, 1982,12,353).Levamisole can modulate PGE2-induced contractions in isolated ileum O,f guinea-pig (Capasso et el., Prosta~landins,1982,23,~27).That*s why we tested Levamisole in isolated tracheal rat rings, p r e c o n ~ r a c t e d by either K + 40 mM or Carbaohol 10" MeThe experiments were carried out in Krebs-He~seleit solutlon,aerated continuously w i t h 0~ 95~ andre02 5~,in the presence of IndometBaoin 10 "~ M. In.the plateau o£ K A0 m M and Csrbachol 10 "> M-induced contractions Levamisole was ~8~inister~d in a oumulatlve fashion (I0~ M to 10" M).The c o n c e n t r a t i o n of 3x10"JM had an effect of a p p r o x i m a t l v e l y 50~ in relaxing+ the p r e c o n t r a c t e d rat trachea by either K 40 mM and stonier.The m o l e c u l a r mechanisms of these rslaxlng effects of Lavamlsole on trachea remain to be defined.
Baiardi #, G. Bovio°; M. Dossena* * Institute of P h a r m a c o l o g y , F a c u l t y of S c i e n c e , University of Pavia, Pavia, Italy ° D i v i s i o n of N e p h r o l o g y , § S er v i ce of N u t r i t i o n a l Pathophysiology, # Medical Informatics Unit, Clinica del Lavoro Foundation, IRCCS, Pavia
Chronic Renal Failure (CRF) is generally characterized by muscle wasting and weakness with a consequent reduction of exercise capacity. The aim of this study was to define the possible cellular alterations by investigating energy mediators and the main metabolic e n e r g y pathways in a group of Chronicallyuremic patients. A needle biopsy was performed in the femoral quadriceps muscle of 25 pre-dialyzed patients with CRF and 12 normal subjects as a control group. The maximum rate (Vmax) of some key enzymes of metabolic pathways and energy mediators concentrations were determined spectrophotometrically. The patient group showed a significant decrease in ATP and creatine phosphate levels, as well as an increase in the Vmax ofhexokinase, citrate synthase, succinate dehydrogenase, malate dehydrogenase, aspartate aminotransferase and alanine a m i n o t r a n s f e r a s e and total NADH cytochrome c reductase; in contrast there was a decrease in pyruvate kinase and cytochrome oxidase activity. The significant modifications of muscle metabolic pathways observed could partly explain the underlying myopathy with consectuent impaired exercise tolerance in CRF patients.
This study was undertaken to determine the effect of propofol on sympathetic neurotransmission in the isolated rat vas deferens. Propofol (10 -6 to 10"4) reversibly reduced the contractile responses induced by exogenously aplied noradrenaline. The contractions evoked in the vas deferens by electrical field stimulation(EFS) did not change by propofol (10 -6 to 10 -5 M),but at 10 -4 M propofol significantly increased contractil responses of EFS. Mephiramine, atropine, methisergid, indomethaein, did not change the contractil responses of propofol to EFS. These results suggest that propofol (i0 -4 M) facilitates sympathetic neurotransmission in rat vas deferens by inhibiting neuronal uptake of the neurotransmitter in sympathetic nerve endings. In the other hand, effect of propofol (10 -6 to 10-4 M) to exogenously applied noradrenaline may be explained by modulation of the postsinaptic effect.
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A L T E R A T E D MUSCLE ENERGY METABOLISM IN PATIENTS WITH CHRONIC RENAL FAILURE. O. Pastoris*, P. Foppa*, M. Catapano*, R. Aquilani§, P.
THE EFFECTS OF LEVAMISOLE ON RAT T R A C H E A L ISOLATED RINGS M.. Costulaanu, Et Teelarlu, C. Filip, A.Negru and Me N e c h i f o r Department of Pharmacology, University of Medloine and Pharmacy, University Street 16 R0-6600, Iasi, Romania
EFFECTS OF PROPOFOL ON SYMPHATETIC NEUROTRANSMISSION IN THE ISOLATED RAT VAS DEFERENS T. Kaya_, Y. Sarioglu, T. Utkarg C. Mimaroglu and K. Yildirim Cumhuriyet University, Faculty of Medicine, Department of Pharmacology, 58140, Sivas, Turkey.
L e v e m i s o l o , a widely used antiholmintio drug,has been shown to restore cutaneousdelayed h y p e r s e n s i t i v i t y in anerglc patients and t o a m p l i f y t h e a c t i v a t i o n of T lymphocytes by in vitro mltogans (Takl st al.,I-
mmtmopharmacol.Immunotoxicol.,1994,16,129), Levamisole can increase the cGMP levels in inflammatory ceXls (Roch-Arveiller et el., Agents Actlons, 1982,12,353).Levamisole can modulate PGE2-induced contractions in isolated ileum O,f guinea-pig (Capasso et el., Prosta~landins,1982,23,~27).That*s why we tested Levamisole in isolated tracheal rat rings, p r e c o n ~ r a c t e d by either K + 40 mM or Carbaohol 10" MeThe experiments were carried out in Krebs-He~seleit solutlon,aerated continuously w i t h 0~ 95~ andre02 5~,in the presence of IndometBaoin 10 "~ M. In.the plateau o£ K A0 m M and Csrbachol 10 "> M-induced contractions Levamisole was ~8~inister~d in a oumulatlve fashion (I0~ M to 10" M).The c o n c e n t r a t i o n of 3x10"JM had an effect of a p p r o x i m a t l v e l y 50~ in relaxing+ the p r e c o n t r a c t e d rat trachea by either K 40 mM and stonier.The m o l e c u l a r mechanisms of these rslaxlng effects of Lavamlsole on trachea remain to be defined.
Baiardi #, G. Bovio°; M. Dossena* * Institute of P h a r m a c o l o g y , F a c u l t y of S c i e n c e , University of Pavia, Pavia, Italy ° D i v i s i o n of N e p h r o l o g y , § S er v i ce of N u t r i t i o n a l Pathophysiology, # Medical Informatics Unit, Clinica del Lavoro Foundation, IRCCS, Pavia
Chronic Renal Failure (CRF) is generally characterized by muscle wasting and weakness with a consequent reduction of exercise capacity. The aim of this study was to define the possible cellular alterations by investigating energy mediators and the main metabolic e n e r g y pathways in a group of Chronicallyuremic patients. A needle biopsy was performed in the femoral quadriceps muscle of 25 pre-dialyzed patients with CRF and 12 normal subjects as a control group. The maximum rate (Vmax) of some key enzymes of metabolic pathways and energy mediators concentrations were determined spectrophotometrically. The patient group showed a significant decrease in ATP and creatine phosphate levels, as well as an increase in the Vmax ofhexokinase, citrate synthase, succinate dehydrogenase, malate dehydrogenase, aspartate aminotransferase and alanine a m i n o t r a n s f e r a s e and total NADH cytochrome c reductase; in contrast there was a decrease in pyruvate kinase and cytochrome oxidase activity. The significant modifications of muscle metabolic pathways observed could partly explain the underlying myopathy with consectuent impaired exercise tolerance in CRF patients.
This study was undertaken to determine the effect of propofol on sympathetic neurotransmission in the isolated rat vas deferens. Propofol (10 -6 to 10"4) reversibly reduced the contractile responses induced by exogenously aplied noradrenaline. The contractions evoked in the vas deferens by electrical field stimulation(EFS) did not change by propofol (10 -6 to 10 -5 M),but at 10 -4 M propofol significantly increased contractil responses of EFS. Mephiramine, atropine, methisergid, indomethaein, did not change the contractil responses of propofol to EFS. These results suggest that propofol (i0 -4 M) facilitates sympathetic neurotransmission in rat vas deferens by inhibiting neuronal uptake of the neurotransmitter in sympathetic nerve endings. In the other hand, effect of propofol (10 -6 to 10-4 M) to exogenously applied noradrenaline may be explained by modulation of the postsinaptic effect.
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