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3-mercaptopyruvate sulfurtransferase activity in brain and liver in the mouse
Poster session I
been emphasised In the recent literature. In the central nervous system NO Is supposed to be the retrograde messenger In those parts which are connected with memory fixation and retention. Presumably we may suggest that behavioral changes reported above could be a result of excessive NO amount In the brain.
I brain and liver In the mouse
114-141 3-mercaptopyruvate sulfurtransferase activity In Y. Katz 1.2, V. Gazit' , D. Ben-Shachar '. ' Bruce Rappaport Faculty of Madlclne. Technion-Israel Institute of Technology. Haifa, Israel. 2 Department of Anesthesiology. Ha'Emek Medical Center, Afula, Israel Cysteine (Cys) is degraded via two pathways, a direct oxidative (Cys sulfinate) and a transamination (3-mercaptopyruvate) pathway. The latter is carried out by the enzyme 3-mercaptopyruvate sulfurtransferase (3-MPST). In the rat, high activities are present in the liver, kidney, erythrocytes, adrenal cortex, and heart, but are low In the brain. Methods: We determined the activity of 3-MPST activatorsllnhibitors In mouse brain and liver. Neonatal ICR mice (4-10 g) were injected subcu• taneously with L-Cys (1.5 mglg body weight) as well as with vitamin K, (2.5 mgfg) and oxoglutarate (2.5 mglg), which are activators of 3-MPST; oxobutyrate (2.5 mglg), an Inhibitor of 3-MPST; and 0.9% NaCI as control (Clln. Chim. Acta 51: 205-210,1974). Results: 3-MPST activity in the brain and liver was 1209 and 1440 Ilmol pyruvate, respectively, formed per gram of fresh tissue per 15 minutes. Peak activity was reached 30 min after L-Cys administration, was maintained for 60 min more, and then decreased gradually. Vitamin K, and oxoglutarate augmented 3-MPST activity 2- to 4-fold in the brain and 1.5- to 2-fold In the liver, compared to control. Oxobutyrate decreased enzyme activity by 50% in both brain and liver. Conclusions: This study shows high enzyme activity in the mouse brain, similar to that in the liver. Further studies are needed to determine the animal species relevant to human brain 3-MPST activity.
114-1421 Early acceleration of antidepressant with plndolol Is sustained at six months M.B. Tome, M.T. Isaac. Department of Psychiatry, Guy~ Hospital, London, England Objective: for the first time to describe the longer-term follow-up of augmen• tation of the antidepressant paroxetine with pindolol, a 5HT'A autoreceptor blocker, in a double blind, randomised, placebo-controlled trial. Method: eighty out-patients (mean age 36 [range 19-£5], 48 female, 32 male) were recruited as described by Tome et al. (1996), each patient receiving paroxetine (20 mg o.d.) plus, randomly, either pindolol (2.5 mg td.s.) or placebo for six weeks. Paroxetlne (open label) was offered to all patients for a further 18 weeks. Follow-up assessments of sixty-nine patients, using the Global Impression [GI]; Montgomery-Asberg Depression Rating scale [MADRS]; Beck Depression Inventory [BDI], took place at weeks 8, 16 and 24. Results: patients originally treated with pindolol (n =32) showed signif• Icantly better clinical outcome at week 24. when compared with patients originally talking paroxetine alone, whether they complied fUlly with follow-up treatment or not. Compliance with follow-up treatment had a significant positive effect on outcome at weeks 16 and 24 in those parents originally treated with paroxetine alone (n =37). Conclusions: The acceleration of the antidepressant effects of paroxetine observed with six weeks' administration of pindolol are sustained in the longer term. The clinical and economic potential Is considerable, and further large scale studies are warranted.
114-1431 Effects of haloperidol and sulpiride on changes In spontaneous EEG and locomotor activity In the delirium model rats treated with ketamlne Y. Mizukl, M. Suetsugl', I. UShlJlma I, M. Yamada '. M. Suzuki 2 , M. Yamamoto 2. Shimonosekl Hospital of Brain Disorders, Shlmonosekl, Japan. ' Dept. of Neuropsychlat.• Yamaguchi Uni~ Sch. of Me~.• Ube. Japan, 2Clln. Pharmacal. Res. Lab., Yamanouch, PharmaceutIcal Co.• Ltd., Tokyo, Japan Delirium Is often observed in the geriatric patients, and could be induced by various drugs such as hypnotics and cholinolytics. In the present study, the
BIOL. PSYCHIATRY 1997:42:1S-297S
478
effects of haloperidol and sulpiride on the EEG- and locomotion-changes produced by ketamine were Investigated. Male Wistar rats weighing about 250 g were used. Vehicle, ketamine (60 mgfkg) and vehicle, ketamlne and haloperidol (0.03, 0.1 and 0.3 mgfkg) or ketamine and sulpirlde (10 mgfkg and 100 mgfkg) were administered Intraperltoneally. Ketamine synchronized cortical EEG and desynchronized hippocampal EEG In a dOSe-dependent manner indicating that the drug induced dissociation between the cortical and hippocampal EEG. These EEG changes were accompanied by an increase in spontaneous locomotor activity, which involved lack of focused direction, stereotypy, irritability and other abnormalities. Both drugs reversed the dissociation between the cortical and hippocampal EEG in ketamine-treated rats. Haloperidol suppressed hyperlocomotion produced by ketamine, but sulpirlde failed to affect the hyperlocomotion. These results suggest that the ketamlne-treated rats could be a conventional model for investigating the pathogenesis of delirium, and that the amelioration of delirium in this model is closely related to the Inhibition of 0, receptors as well as 02 receptors.
114-1441 Potentiation of morphine analgesia and Inhibition
of dependence development by Ca2+ channel antagonists J. Michaluk, B. Karolewicz, L Antklewicz-Michaluk, J. Vetulanl. Institute of Pharmacology. Polish Academy of Sciences. Krak6w. Poland
We have previously found that nifedipine potentiates morphine analgesia and prevents the development of dependence after chronic morphine treatments. Presently we compared the effect of nifediplne with other L-type Ca2+ channel (LCC) antagonists, nimodipine (a dihydropyridine) and verapamil (a phenylethylalkylamine). Methods: Male Wistar rats were used throughout. To assess the effect of LCC blockade, the compounds were given always 30 min before morphine administration. Morphine analgesia after a single dose was measured in a hot plate test; the development of dependence was assessed by naloxone precipitation test after 13 days of morphine (20-30 mgfkg Ip) administration. LCC were assayed in the cerebral cortex as [3H]nitrendipine binding sites. Blood pressure was monitored bloodlessly from the tail. Results: All the LCC antagonists, potentiated morphine analgesia (also of morphine subthreshold doses), nifedipine and verapamil being more effective than nimodipine. Their administration during chronic morphine treatment prevented development of morphine dependence as reflected by causing naloxone unable to precipitate withdrawal syndrome. Nifedipine was the most potent In inhibition of both body shakes and weight loss; verapamil was the least effective but its effect was nevertheless significant. While chronic morphine up regulated LCC, the coadministration of LCC antagonists completely prevented this effect. The doses of LCe antagonists used did not produced hypotension.
114-1451 Antidepressant effects on GTP-blnding proteins In C-6 glioma cells and natural killer lymphocytes H. KavaN " A. Fi~erova 2, V. Usa 3, F. KOVaN 4, Z. Fi§ar', I. Malbohan ' • , 1st Mad. Fac., Charles Unlv. Prague. Sma, Czech Rep, 2 fnst. Microbiol. Bma. Czech Rep, 3/nst. Physlol. Acad. Sci., Prague, Bmo. Czech Rep, 4 Unlv. Vet. Pharm. SC/., Bma, Czech Rep Abnormalities in cell signal transduction are associated with antidepressant (AD) effects before and during treatment of depressive disorders. Question is how ADs act at the level of various Ga subunit expression (Gaq/l1 , Gas and Gail,2) in trlmerlc GTP- binding proteins. Our aim was to use in vitro models (C-6 cells, human natural killer (NK) lymphocytes and rat NK cell line RNK 16) for studies of pharmacologically different AD effects on Ga expression changes using ELISA and Western blotting with own antibodies. Our attention was focused on different effects of TCA and SSRI ADs on changes In Ga subunits. We demonstrated characteristic pattems of changes in various Ga expressions for different AD, namely amitriptyline and fluoxetine, In both C-6 glioma cells and human NK cells based on alterations of Gaq/l1 In contrast to no change in RNK 16 besides of altered levels of Gas and Gai1,2 in all tested cells. Similarities in Gaq/11 expressions in C-6 and human NK cells could be related to effector phospholipase C pathways. Results will be discussed also in relationship to AD influence via purlnergic receptors, which are linked to GTP-bindlng proteins.
been emphasised In the recent literature. In the central nervous system NO Is supposed to be the retrograde messenger In those parts which are connected with memory fixation and retention. Presumably we may suggest that behavioral changes reported above could be a result of excessive NO amount In the brain.
I brain and liver In the mouse
114-141 3-mercaptopyruvate sulfurtransferase activity In Y. Katz 1.2, V. Gazit' , D. Ben-Shachar '. ' Bruce Rappaport Faculty of Madlclne. Technion-Israel Institute of Technology. Haifa, Israel. 2 Department of Anesthesiology. Ha'Emek Medical Center, Afula, Israel Cysteine (Cys) is degraded via two pathways, a direct oxidative (Cys sulfinate) and a transamination (3-mercaptopyruvate) pathway. The latter is carried out by the enzyme 3-mercaptopyruvate sulfurtransferase (3-MPST). In the rat, high activities are present in the liver, kidney, erythrocytes, adrenal cortex, and heart, but are low In the brain. Methods: We determined the activity of 3-MPST activatorsllnhibitors In mouse brain and liver. Neonatal ICR mice (4-10 g) were injected subcu• taneously with L-Cys (1.5 mglg body weight) as well as with vitamin K, (2.5 mgfg) and oxoglutarate (2.5 mglg), which are activators of 3-MPST; oxobutyrate (2.5 mglg), an Inhibitor of 3-MPST; and 0.9% NaCI as control (Clln. Chim. Acta 51: 205-210,1974). Results: 3-MPST activity in the brain and liver was 1209 and 1440 Ilmol pyruvate, respectively, formed per gram of fresh tissue per 15 minutes. Peak activity was reached 30 min after L-Cys administration, was maintained for 60 min more, and then decreased gradually. Vitamin K, and oxoglutarate augmented 3-MPST activity 2- to 4-fold in the brain and 1.5- to 2-fold In the liver, compared to control. Oxobutyrate decreased enzyme activity by 50% in both brain and liver. Conclusions: This study shows high enzyme activity in the mouse brain, similar to that in the liver. Further studies are needed to determine the animal species relevant to human brain 3-MPST activity.
114-1421 Early acceleration of antidepressant with plndolol Is sustained at six months M.B. Tome, M.T. Isaac. Department of Psychiatry, Guy~ Hospital, London, England Objective: for the first time to describe the longer-term follow-up of augmen• tation of the antidepressant paroxetine with pindolol, a 5HT'A autoreceptor blocker, in a double blind, randomised, placebo-controlled trial. Method: eighty out-patients (mean age 36 [range 19-£5], 48 female, 32 male) were recruited as described by Tome et al. (1996), each patient receiving paroxetine (20 mg o.d.) plus, randomly, either pindolol (2.5 mg td.s.) or placebo for six weeks. Paroxetlne (open label) was offered to all patients for a further 18 weeks. Follow-up assessments of sixty-nine patients, using the Global Impression [GI]; Montgomery-Asberg Depression Rating scale [MADRS]; Beck Depression Inventory [BDI], took place at weeks 8, 16 and 24. Results: patients originally treated with pindolol (n =32) showed signif• Icantly better clinical outcome at week 24. when compared with patients originally talking paroxetine alone, whether they complied fUlly with follow-up treatment or not. Compliance with follow-up treatment had a significant positive effect on outcome at weeks 16 and 24 in those parents originally treated with paroxetine alone (n =37). Conclusions: The acceleration of the antidepressant effects of paroxetine observed with six weeks' administration of pindolol are sustained in the longer term. The clinical and economic potential Is considerable, and further large scale studies are warranted.
114-1431 Effects of haloperidol and sulpiride on changes In spontaneous EEG and locomotor activity In the delirium model rats treated with ketamlne Y. Mizukl, M. Suetsugl', I. UShlJlma I, M. Yamada '. M. Suzuki 2 , M. Yamamoto 2. Shimonosekl Hospital of Brain Disorders, Shlmonosekl, Japan. ' Dept. of Neuropsychlat.• Yamaguchi Uni~ Sch. of Me~.• Ube. Japan, 2Clln. Pharmacal. Res. Lab., Yamanouch, PharmaceutIcal Co.• Ltd., Tokyo, Japan Delirium Is often observed in the geriatric patients, and could be induced by various drugs such as hypnotics and cholinolytics. In the present study, the
BIOL. PSYCHIATRY 1997:42:1S-297S
478
effects of haloperidol and sulpiride on the EEG- and locomotion-changes produced by ketamine were Investigated. Male Wistar rats weighing about 250 g were used. Vehicle, ketamine (60 mgfkg) and vehicle, ketamlne and haloperidol (0.03, 0.1 and 0.3 mgfkg) or ketamine and sulpirlde (10 mgfkg and 100 mgfkg) were administered Intraperltoneally. Ketamine synchronized cortical EEG and desynchronized hippocampal EEG In a dOSe-dependent manner indicating that the drug induced dissociation between the cortical and hippocampal EEG. These EEG changes were accompanied by an increase in spontaneous locomotor activity, which involved lack of focused direction, stereotypy, irritability and other abnormalities. Both drugs reversed the dissociation between the cortical and hippocampal EEG in ketamine-treated rats. Haloperidol suppressed hyperlocomotion produced by ketamine, but sulpirlde failed to affect the hyperlocomotion. These results suggest that the ketamlne-treated rats could be a conventional model for investigating the pathogenesis of delirium, and that the amelioration of delirium in this model is closely related to the Inhibition of 0, receptors as well as 02 receptors.
114-1441 Potentiation of morphine analgesia and Inhibition
of dependence development by Ca2+ channel antagonists J. Michaluk, B. Karolewicz, L Antklewicz-Michaluk, J. Vetulanl. Institute of Pharmacology. Polish Academy of Sciences. Krak6w. Poland
We have previously found that nifedipine potentiates morphine analgesia and prevents the development of dependence after chronic morphine treatments. Presently we compared the effect of nifediplne with other L-type Ca2+ channel (LCC) antagonists, nimodipine (a dihydropyridine) and verapamil (a phenylethylalkylamine). Methods: Male Wistar rats were used throughout. To assess the effect of LCC blockade, the compounds were given always 30 min before morphine administration. Morphine analgesia after a single dose was measured in a hot plate test; the development of dependence was assessed by naloxone precipitation test after 13 days of morphine (20-30 mgfkg Ip) administration. LCC were assayed in the cerebral cortex as [3H]nitrendipine binding sites. Blood pressure was monitored bloodlessly from the tail. Results: All the LCC antagonists, potentiated morphine analgesia (also of morphine subthreshold doses), nifedipine and verapamil being more effective than nimodipine. Their administration during chronic morphine treatment prevented development of morphine dependence as reflected by causing naloxone unable to precipitate withdrawal syndrome. Nifedipine was the most potent In inhibition of both body shakes and weight loss; verapamil was the least effective but its effect was nevertheless significant. While chronic morphine up regulated LCC, the coadministration of LCC antagonists completely prevented this effect. The doses of LCe antagonists used did not produced hypotension.
114-1451 Antidepressant effects on GTP-blnding proteins In C-6 glioma cells and natural killer lymphocytes H. KavaN " A. Fi~erova 2, V. Usa 3, F. KOVaN 4, Z. Fi§ar', I. Malbohan ' • , 1st Mad. Fac., Charles Unlv. Prague. Sma, Czech Rep, 2 fnst. Microbiol. Bma. Czech Rep, 3/nst. Physlol. Acad. Sci., Prague, Bmo. Czech Rep, 4 Unlv. Vet. Pharm. SC/., Bma, Czech Rep Abnormalities in cell signal transduction are associated with antidepressant (AD) effects before and during treatment of depressive disorders. Question is how ADs act at the level of various Ga subunit expression (Gaq/l1 , Gas and Gail,2) in trlmerlc GTP- binding proteins. Our aim was to use in vitro models (C-6 cells, human natural killer (NK) lymphocytes and rat NK cell line RNK 16) for studies of pharmacologically different AD effects on Ga expression changes using ELISA and Western blotting with own antibodies. Our attention was focused on different effects of TCA and SSRI ADs on changes In Ga subunits. We demonstrated characteristic pattems of changes in various Ga expressions for different AD, namely amitriptyline and fluoxetine, In both C-6 glioma cells and human NK cells based on alterations of Gaq/l1 In contrast to no change in RNK 16 besides of altered levels of Gas and Gai1,2 in all tested cells. Similarities in Gaq/11 expressions in C-6 and human NK cells could be related to effector phospholipase C pathways. Results will be discussed also in relationship to AD influence via purlnergic receptors, which are linked to GTP-bindlng proteins.