The Experts below are selected from a list of 186 Experts worldwide ranked by ideXlab platform
Lucio G. Costa - One of the best experts on this subject based on the ideXlab platform.
-
INTERACTION OF ETHANOL AND ANOXIA WITH MUSCARINIC RECEPTOR : STIMULATED Phosphoinositide Metabolism DURING BRAIN DEVELOPMENT
Life sciences, 1995Co-Authors: Walter Balduini, F. Reno, Lucio G. CostaAbstract:The mechanism(s) by which ethanol induces alterations in brain development may involve direct actions (e.g. changes in specific biochemical pathways), or indirect effects, such as cerebral hypoxia resulting from ethanol - induced circulatory changes. Since both ethanol and hypoxia are known to affect the Metabolism of Phosphoinositides, which has been suggested as a possible target for ethanol's developmental neurotoxicity, in the present study we have investigated the in vitro effects of both severe hypoxia (anoxia) and ethanol (alone or in combination) on muscarinic receptor-stimulated Phosphoinositide Metabolism in cerebral cortex slices from neonatal rats. Anoxia markedly inhibited carbachol - stimulated Phosphoinositide Metabolism in adult rats (67%), but only slightly (10%) in neonatal animals. Reoxygenation reversed the effect of anoxia at both ages. On the other hand, ethanol's inhibitory effect was pronounced in neonatal rats only, and was additive to that of anoxia. The presence of ethanol did not affect the recovery of carbachol - stimulated Phosphoinositide Metabolism following anoxia and reoxygenation. These results indicate that ethanol and anoxia differently and independently affect muscarinic receptor - stimulated Phosphoinositide Metabolism and may mutually contribute to the CNS effects observed following developmental ethanol exposure.
-
Inhibition of muscarinic receptor-stimulated Phosphoinositide Metabolism by cocaine, norcocaine and cocaethylene in rat brain
Brain research. Developmental brain research, 1994Co-Authors: Xiaoxia Tan, Lucio G. CostaAbstract:Abstract The interaction of cocaine, its metabolites norcocaine and benzoylecgonine, and cocaethylene, which is formed following a combined cocaine and ethanol exposure, with muscarinic receptor binding and Phosphoinositide Metabolism was investigated in brain from immature rats. Cocaine and norcocaine inhibited binding of [3H]telenzepine and carbachol-stimulated Phosphoinositide Metabolism in cerebral cortex, while benzoylecgonine was devoid of any inhibitory activity. Cocaethylene was the most potent inhibitor of both binding and Phosphoinositide Metabolism. The effect of cocaine was more pronounced at the muscarinic receptors, but a small inhibition of histamine — and serotonin — stimulated Phosphoinositide Metabolism was also observed.
-
Administration of ethanol during brain growth spurt causes dose-dependent microencephaly and inhibition of muscarinic receptor-stimulated Phosphoinositide Metabolism in the rat
1994Co-Authors: F. Reno, Walter Balduini, X X Tan, Lucio G. CostaAbstract:Different dose levels of ethanol (2,3,4,5 g/kg were administered to rat pups between postnatal days 4 and 10. Ethanol caused a dose - dependent decrease in brain weight (measured on postnatal day 12) and inhibition of carbachol - stimulated Phosphoinositide Metabolism (measured in cerebral cortex slices on postnatal day 7). The 2 g/kg dose, which gave blood alcohol levels of 128 mg/dl, was a no-effect-level for both endpoints. Ethanol administration did not alter the relative distribution of Phosphoinositides in the cerebral cortex from 7 day - old rats. These results show a dose - dependent correlation between ethanol - induced microencephaly and inhibition of muscarinic receptor - stimulated Phosphoinositide Metabolism and add support the hypothesis that this second messenger system may be involved in the developmental neurotoxicity of ethanol
-
Regional development of carbachol-, glutamate-, norepinephrine-, and serotonin-stimulated Phosphoinositide Metabolism in rat brain
Brain research. Developmental brain research, 1991Co-Authors: Walter Balduini, Stefano M. Candura, Lucio G. CostaAbstract:Abstract Phosphoinositide Metabolism stimulated by activation of cholinergic muscarinic, glutamatergic, α-adrenergic and serotoninergic receptors was measured in brain regions of the developing rats. Accumulation of [3H]inositol phosphates ([3H]InsPs) in [3H]inositol-prelabeled slices from cerebral cortex, hippocampus, brainstem and cerebellum was measured as an index of Phosphoinositide Metabolism. Large age-, neurotransmitter receptor-, and brain region-dependent differences were found. Carbachol-stimulated [3H]InsPs accumulation peaked on postnatal day 7 in cerebral cortex and hippocampus while in cerebellum and brainstem the effect of muscarinic stimulation was maximal at birth and then declined to adulthood. The effect of glutamate also showed a peak on day 7 in hippocampus and brainstem and a developmentally related decrease in cerebral cortex. In the cerebellum, on the other hand, the response to glutamate remained sustained through adulthood. Stimulation of Phosphoinositide Metabolism by norepinephrine increased with age in hippocampus and cerebral cortex, but decreased in the cerebellum, while the effect of serotonin did not change significantly with age except in cerebellum. These changes in receptor-stimulated Phosphoinositide Metabolism do not parallel, for the most part, the ontogeny of receptor recognition sites. Activation of the Phosphoinositide Metabolism pathway leads to an increase in intracellular calcium levels and to stimulation of protein kinase C, which are believed to play significant roles in cellular proliferation and differentiation. Thus, the differential ability of neurotransmitters to stimulate Phosphoinositide hydrolysis might play a role in the development of brain regions.
-
Interaction of short chain aliphatic alcohols with muscarinic receptor-stimulated Phosphoinositide Metabolism in cerebral cortex from neonatal and adult rats.
Neurotoxicology, 1991Co-Authors: Stefano M. Candura, Walter Balduini, Lucio G. CostaAbstract:Muscarinic receptor-stimulated Phosphoinositide Metabolism has been recently suggested as a possible target for the neurotoxic effects of ethanol during brain development. Since two other alcohols, tertiary butanol and n-propanol, have been shown to cause microencephaly in the rat when administered during the brain growth spurt, in the present study we investigated the in vitro effects of five short chain aliphatic alcohols on muscarinic receptor-stimulated Phosphoinositide Metabolism in cerebral cortical slices from 7 day-old rats. In neonatal animals all alcohols tested inhibited carbachol (1 mM)-stimulated [3H]inositol phosphates accumulation in a dose- and time-dependent manner. The order of potency was t-butanol greater than n-propanol greater than or equal to iso-propanol greater than ethanol greater than methanol. After 90 min of incubation, ethanol, n-propanol and t-butanol caused a significant inhibition of muscarinic receptor-stimulated inositol Metabolism at doses as low as 15 - 50 mM, comparable to the blood concentrations reached after in vivo administration of doses able to induce developmental neurotoxicity. The inhibitory effect of ethanol was additive to that of iso-propanol or t-butanol. Differently from these effects in 7 day-old rats, in cortical slices from adult animals methanol and ethanol had no effect on carbachol-stimulated Phosphoinositide Metabolism, while the two propanol isomers and t-butanol were less effective than in neonatal animals. These results suggest that muscarinic receptor-coupled Phosphoinositide Metabolism might be a common neurochemical target for the developmental neurotoxicity of short chain aliphatic alcohols.
Walter Balduini - One of the best experts on this subject based on the ideXlab platform.
-
INTERACTION OF ETHANOL AND ANOXIA WITH MUSCARINIC RECEPTOR : STIMULATED Phosphoinositide Metabolism DURING BRAIN DEVELOPMENT
Life sciences, 1995Co-Authors: Walter Balduini, F. Reno, Lucio G. CostaAbstract:The mechanism(s) by which ethanol induces alterations in brain development may involve direct actions (e.g. changes in specific biochemical pathways), or indirect effects, such as cerebral hypoxia resulting from ethanol - induced circulatory changes. Since both ethanol and hypoxia are known to affect the Metabolism of Phosphoinositides, which has been suggested as a possible target for ethanol's developmental neurotoxicity, in the present study we have investigated the in vitro effects of both severe hypoxia (anoxia) and ethanol (alone or in combination) on muscarinic receptor-stimulated Phosphoinositide Metabolism in cerebral cortex slices from neonatal rats. Anoxia markedly inhibited carbachol - stimulated Phosphoinositide Metabolism in adult rats (67%), but only slightly (10%) in neonatal animals. Reoxygenation reversed the effect of anoxia at both ages. On the other hand, ethanol's inhibitory effect was pronounced in neonatal rats only, and was additive to that of anoxia. The presence of ethanol did not affect the recovery of carbachol - stimulated Phosphoinositide Metabolism following anoxia and reoxygenation. These results indicate that ethanol and anoxia differently and independently affect muscarinic receptor - stimulated Phosphoinositide Metabolism and may mutually contribute to the CNS effects observed following developmental ethanol exposure.
-
Effect of prenatal treatment with methylazoxymethanol on carbachol-, norepinephrine- and glutamate-stimulated Phosphoinositide Metabolism in the neonatal, young, and adult offspring
Neurochemical research, 1995Co-Authors: Walter Balduini, G. Lombardelli, G. Peruzzi, Flaminio CattabeniAbstract:Carbachol-, norepinephrine- and glutamate-stimulated Phosphoinositide Metabolism was investigated in the neonatal, young and adult cerebral cortex slices of rats prenatally treated with methylazoxymethanol (MAM) on gestational day 15 (GD15) or GD19. In rat offspring treated on GD15 there was a significant reduction in the accumulation of [3H]inositol phosphates induced by carbachol and a significant increase in the accumulation of [3H]inositol phosphates induced by norepinephrine on day 7, whereas no changes were observed at the other ages. No significant changes, on the other hand, were observed for glutamate-stimulated Phosphoinositide Metabolism in GD15 treated rats and for carbachol-, norepinephrine- and glutamate-stimulated Phosphoinositide Metabolism in animals treated on GD19 at any of the different ages evaluated. These results indicate that treatment with MAM on GD15, which results in a marked microencephaly, causes a marked alteration of muscarinic and α1-adrenergic receptor-stimulated Phosphoinositide Metabolism during brain development and that these alterations undergo adaptive changes in the adult brain.
-
Administration of ethanol during brain growth spurt causes dose-dependent microencephaly and inhibition of muscarinic receptor-stimulated Phosphoinositide Metabolism in the rat
1994Co-Authors: F. Reno, Walter Balduini, X X Tan, Lucio G. CostaAbstract:Different dose levels of ethanol (2,3,4,5 g/kg were administered to rat pups between postnatal days 4 and 10. Ethanol caused a dose - dependent decrease in brain weight (measured on postnatal day 12) and inhibition of carbachol - stimulated Phosphoinositide Metabolism (measured in cerebral cortex slices on postnatal day 7). The 2 g/kg dose, which gave blood alcohol levels of 128 mg/dl, was a no-effect-level for both endpoints. Ethanol administration did not alter the relative distribution of Phosphoinositides in the cerebral cortex from 7 day - old rats. These results show a dose - dependent correlation between ethanol - induced microencephaly and inhibition of muscarinic receptor - stimulated Phosphoinositide Metabolism and add support the hypothesis that this second messenger system may be involved in the developmental neurotoxicity of ethanol
-
Cholinergic hyperinnervation in the cerebral cortex of microencephalic rats does not result in muscarinic receptor down-regulation or in alteration of receptor-stimulated Phosphoinositide Metabolism
Neurochemical Research, 1992Co-Authors: Walter Balduini, Gabriella Lombardelli, Guidubaldo Peruzzi, Flaminio CattabeniAbstract:Administration of methylazoxymethanol (MAM; 25 mg/kg) to pregnant rats at gestational day 15 (GD 15) induces a marked reduction of telencephalic areas of the offspring brain. Previous neurochemical studies demonstrated a marked cholinergic hyperinnervation in the cerebral cortex of microencephalic rats. In this study we have evaluated whether this cholinergic hyperinnervation could result in altered functionality of muscarinic receptors. Acetylcholinesterase activity (AChE) was increased by 69% in the cerebral cortex of MAM treated rats confirming a relative hyperinnervation, whereas in the hippocampus and striatum no significant changes were observed. Despite the marked hyperinnervation, in the cerebral cortex of microencephalic rats neither muscarinic receptor-stimulated Phosphoinositide Metabolism nor muscarinic, receptor density were altered. No differences in receptor density were also observed in the hippocampus and striatum. Chronic diisopropylfluorophosphate (DFP) administration induced a marked decrease of AChE activity and down-regulation of muscarinic receptors whereas atropine administration resulted in receptor up-regulation in cerebral cortex, striatum and hippocampus of both control and MAM rats. The results confirm a relative cholinergic hyperinnervation in the cerebral cortex of microencephalic rats and demonstrate that the regulation of muscarinic receptor-stimulated Phosphoinositide Metabolism and muscarinic receptor plasticity is not modified in a condition of increased cholinergic presynaptic terminals.
-
Regional development of carbachol-, glutamate-, norepinephrine-, and serotonin-stimulated Phosphoinositide Metabolism in rat brain
Brain research. Developmental brain research, 1991Co-Authors: Walter Balduini, Stefano M. Candura, Lucio G. CostaAbstract:Abstract Phosphoinositide Metabolism stimulated by activation of cholinergic muscarinic, glutamatergic, α-adrenergic and serotoninergic receptors was measured in brain regions of the developing rats. Accumulation of [3H]inositol phosphates ([3H]InsPs) in [3H]inositol-prelabeled slices from cerebral cortex, hippocampus, brainstem and cerebellum was measured as an index of Phosphoinositide Metabolism. Large age-, neurotransmitter receptor-, and brain region-dependent differences were found. Carbachol-stimulated [3H]InsPs accumulation peaked on postnatal day 7 in cerebral cortex and hippocampus while in cerebellum and brainstem the effect of muscarinic stimulation was maximal at birth and then declined to adulthood. The effect of glutamate also showed a peak on day 7 in hippocampus and brainstem and a developmentally related decrease in cerebral cortex. In the cerebellum, on the other hand, the response to glutamate remained sustained through adulthood. Stimulation of Phosphoinositide Metabolism by norepinephrine increased with age in hippocampus and cerebral cortex, but decreased in the cerebellum, while the effect of serotonin did not change significantly with age except in cerebellum. These changes in receptor-stimulated Phosphoinositide Metabolism do not parallel, for the most part, the ontogeny of receptor recognition sites. Activation of the Phosphoinositide Metabolism pathway leads to an increase in intracellular calcium levels and to stimulation of protein kinase C, which are believed to play significant roles in cellular proliferation and differentiation. Thus, the differential ability of neurotransmitters to stimulate Phosphoinositide hydrolysis might play a role in the development of brain regions.
Flaminio Cattabeni - One of the best experts on this subject based on the ideXlab platform.
-
Effect of prenatal treatment with methylazoxymethanol on carbachol-, norepinephrine- and glutamate-stimulated Phosphoinositide Metabolism in the neonatal, young, and adult offspring
Neurochemical research, 1995Co-Authors: Walter Balduini, G. Lombardelli, G. Peruzzi, Flaminio CattabeniAbstract:Carbachol-, norepinephrine- and glutamate-stimulated Phosphoinositide Metabolism was investigated in the neonatal, young and adult cerebral cortex slices of rats prenatally treated with methylazoxymethanol (MAM) on gestational day 15 (GD15) or GD19. In rat offspring treated on GD15 there was a significant reduction in the accumulation of [3H]inositol phosphates induced by carbachol and a significant increase in the accumulation of [3H]inositol phosphates induced by norepinephrine on day 7, whereas no changes were observed at the other ages. No significant changes, on the other hand, were observed for glutamate-stimulated Phosphoinositide Metabolism in GD15 treated rats and for carbachol-, norepinephrine- and glutamate-stimulated Phosphoinositide Metabolism in animals treated on GD19 at any of the different ages evaluated. These results indicate that treatment with MAM on GD15, which results in a marked microencephaly, causes a marked alteration of muscarinic and α1-adrenergic receptor-stimulated Phosphoinositide Metabolism during brain development and that these alterations undergo adaptive changes in the adult brain.
-
Cholinergic hyperinnervation in the cerebral cortex of microencephalic rats does not result in muscarinic receptor down-regulation or in alteration of receptor-stimulated Phosphoinositide Metabolism
Neurochemical Research, 1992Co-Authors: Walter Balduini, Gabriella Lombardelli, Guidubaldo Peruzzi, Flaminio CattabeniAbstract:Administration of methylazoxymethanol (MAM; 25 mg/kg) to pregnant rats at gestational day 15 (GD 15) induces a marked reduction of telencephalic areas of the offspring brain. Previous neurochemical studies demonstrated a marked cholinergic hyperinnervation in the cerebral cortex of microencephalic rats. In this study we have evaluated whether this cholinergic hyperinnervation could result in altered functionality of muscarinic receptors. Acetylcholinesterase activity (AChE) was increased by 69% in the cerebral cortex of MAM treated rats confirming a relative hyperinnervation, whereas in the hippocampus and striatum no significant changes were observed. Despite the marked hyperinnervation, in the cerebral cortex of microencephalic rats neither muscarinic receptor-stimulated Phosphoinositide Metabolism nor muscarinic, receptor density were altered. No differences in receptor density were also observed in the hippocampus and striatum. Chronic diisopropylfluorophosphate (DFP) administration induced a marked decrease of AChE activity and down-regulation of muscarinic receptors whereas atropine administration resulted in receptor up-regulation in cerebral cortex, striatum and hippocampus of both control and MAM rats. The results confirm a relative cholinergic hyperinnervation in the cerebral cortex of microencephalic rats and demonstrate that the regulation of muscarinic receptor-stimulated Phosphoinositide Metabolism and muscarinic receptor plasticity is not modified in a condition of increased cholinergic presynaptic terminals.
-
Time-, concentration-, and age-dependent inhibition of muscarinic receptor-stimulated Phosphoinositide Metabolism by ethanol in the developing rat brain.
Neurochemical research, 1991Co-Authors: Walter Balduini, Stefano M. Candura, Flaminio Cattabeni, L Manzo, Lucio G. CostaAbstract:We have previously reported that administration of ethanol (EtOH; 4 g/Kg/day) to rats from postnatal day 4 to day 10 causes microencephaly and decreases muscarinic receptor-stimulated inositol Metabolism on days 7 and 10 (1). An identical exposure to EtOH of adult rats, which resulted in similar blood EtOH concentrations, did not have any effect on the same system. Initial in vitro studies have shown the presence of a differential sensitivity to EtOH of the Phosphoinositide system coupled to muscarinic receptors during development (2). In the present study we have expanded these findings by investigating the concentration-, time-, and age-dependent effects of EtOH on accumulation of [3H]inositol phosphates ([3H]InsPs) in brain slices. EtOH caused a dose-dependent inhibition of carbachol-stimulated Phosphoinositide Metabolism in cerebral cortex slices from 7 day-old rats. When the time of incubation with EtOH was increased to 90 minutes, concentrations as low as 50 mM, which are reached following in vivo administration of EtOH, significantly inhibited the muscarinic response. The effect of EtOH was rather specific for the muscarinic receptors, since, even with longer incubation times, the accumulation of [3H]InsPs induced by norepinephrine or serotonin was inhibited only at concentrations of 150–500 mM. The effect of EtOH was more pronounced in cerebral cortex, hippocampus and cerebellum, and less in the brainstem. The potency of EtOH in inhibiting carbachol-stimulated Phosphoinositide Metabolism was also dependent on the age of the animals. Its effect was maximal in the 7 day-old rat and less pronounced in younger and older animals. These results confirm that the Phosphoinositide system coupled to muscarinic receptors might represent a relevant target for the developmental neurotoxicity of EtOH.
R. A. John Challiss - One of the best experts on this subject based on the ideXlab platform.
-
Effect of temperature on muscarinic cholinoceptor-mediated Phosphoinositide Metabolism and tension generation in bovine tracheal smooth muscle
Naunyn-Schmiedeberg's Archives of Pharmacology, 1994Co-Authors: Edwin R. Chilvers, R. A. John Challiss, Mark A. Giembycz, Graham J. Offer, Stefan R. NahorskiAbstract:The effect of decreased temperature on Phosphoinositide Metabolism was studied in flurbiprofen pretreated bovine tracheal smooth muscle (BTSM) by investigating the consequences of cooling on muscarinic-cholinoceptor-mediated [^3H]inositol phosphate ([^3H]InsP) and inositol 1,4,5-trisphosphate (Ins(1,4,5)P_3) accumulation, basal phosphoinositidase C (PIC) activity and airways smooth muscle (ASM) tone. Cooling of [^3H]Ins labelled BTSM slices from 37°C to 27°C for 20 min prior to the addition of agonist caused a substantial (73.0±2.5%) inhibition of carbachol (100 μM, 30 min)-stimulated [^3H]InsP accumulation compared to values measured at 37°C. The degree of inhibition of [^3H]InsP accumulation was similar at all agonist time points (2–30 min) studied. In parallel experiments, cooling of unlabelled BTSM slices from 37°C to 27°C resulted in a 34% reduction in basal Ins(1,4,5)P_3 mass (37°C, 13.1±0.6 pmol mg^− protein; 27°C, 8.9±0.9 pmol mg^−1 protein; P
-
Phosphoinositide Metabolism in airway smooth muscle.
Pharmacology & therapeutics, 1994Co-Authors: Edwin R. Chilvers, Barbara J. Lynch, R. A. John ChallissAbstract:Abstract Agonist-stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate, which generates inositol 1,4,5-trisphosphate and sn -1,2-diacylglycerol, is thought to be one of the major mechanisms underlying pharmacomechanical coupling in airway smooth muscle. This article is a review of the currently available information on Phosphoinositide and inositol 1,4,5-trisphophate Metabolism in this tissue and includes data on inositol 1,4,5-trisphophate-induced Ca 2+ release and the receptor mediating this effect. The final section outlines the potential mechanisms underlying physiological regulation of Phosphoinositide Metabolism by other second-messenger pathways operative in this tissue.
Edwin R. Chilvers - One of the best experts on this subject based on the ideXlab platform.
-
Effect of temperature on muscarinic cholinoceptor-mediated Phosphoinositide Metabolism and tension generation in bovine tracheal smooth muscle
Naunyn-Schmiedeberg's Archives of Pharmacology, 1994Co-Authors: Edwin R. Chilvers, R. A. John Challiss, Mark A. Giembycz, Graham J. Offer, Stefan R. NahorskiAbstract:The effect of decreased temperature on Phosphoinositide Metabolism was studied in flurbiprofen pretreated bovine tracheal smooth muscle (BTSM) by investigating the consequences of cooling on muscarinic-cholinoceptor-mediated [^3H]inositol phosphate ([^3H]InsP) and inositol 1,4,5-trisphosphate (Ins(1,4,5)P_3) accumulation, basal phosphoinositidase C (PIC) activity and airways smooth muscle (ASM) tone. Cooling of [^3H]Ins labelled BTSM slices from 37°C to 27°C for 20 min prior to the addition of agonist caused a substantial (73.0±2.5%) inhibition of carbachol (100 μM, 30 min)-stimulated [^3H]InsP accumulation compared to values measured at 37°C. The degree of inhibition of [^3H]InsP accumulation was similar at all agonist time points (2–30 min) studied. In parallel experiments, cooling of unlabelled BTSM slices from 37°C to 27°C resulted in a 34% reduction in basal Ins(1,4,5)P_3 mass (37°C, 13.1±0.6 pmol mg^− protein; 27°C, 8.9±0.9 pmol mg^−1 protein; P
-
Phosphoinositide Metabolism in airway smooth muscle.
Pharmacology & therapeutics, 1994Co-Authors: Edwin R. Chilvers, Barbara J. Lynch, R. A. John ChallissAbstract:Abstract Agonist-stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate, which generates inositol 1,4,5-trisphosphate and sn -1,2-diacylglycerol, is thought to be one of the major mechanisms underlying pharmacomechanical coupling in airway smooth muscle. This article is a review of the currently available information on Phosphoinositide and inositol 1,4,5-trisphophate Metabolism in this tissue and includes data on inositol 1,4,5-trisphophate-induced Ca 2+ release and the receptor mediating this effect. The final section outlines the potential mechanisms underlying physiological regulation of Phosphoinositide Metabolism by other second-messenger pathways operative in this tissue.