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E.a. Zahalka - One of the best experts on this subject based on the ideXlab platform.
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Differential development of Cholinergic Nerve terminal markers in rat brain regions: implications for Nerve terminal density, impulse activity and specific gene expression.
Brain research, 1993Co-Authors: E.a. Zahalka, S.e. Lappi, Joseph Yanai, F J Seidler, T A SlotkinAbstract:During critical developmental periods, Cholinergic activity plays a key role in programming the development of target cells. In the current study, ontogeny of Cholinergic terminals and their activity were contrasted in 4 brain regions of the fetal and neonatal rat using choline acetyltransferase activity, which is unresponsive to changes in impulse flow, and [3H]hemicholinium-3 binding, which labels the high-affinity choline transporter that upregulates in response to increased neuronal stimulation. In all 4 regions (cerebral cortex, midbrain + brainstem, striatum, hippocampus) choline acetyltransferase activity increased markedly from late gestation through young adulthood, but generally did so in parallel with the expansion of total membrane protein, reflective of axonal outgrowth and synaptic proliferation. In contrast, [3H]hemicholinium-3 binding was extremely high in late gestation and immediately after birth, declined in the first postnatal week and then rose again into young adulthood. The ontogenetic changes reflected alterations primarily in the number of binding sites (Bmax) and not in binding affinity. Only the latter phase of development of [3H]hemicholinium-3 binding corresponded to the ontogenetic changes in choline acetyltransferase activity; in the hippocampus, there were disparities even in young adulthood, where [3H]hemicholinium-3 binding showed a spike of activity centered around the 5th to 6th postnatal week, whereas choline acetyltransferase did not. Correction of binding for membrane protein development did not eliminate any of the major differences in developmental patterns between the two markers. These results suggest that development of the choline transporter binding site is regulated independently of the outgrowth of the bulk of Cholinergic Nerve terminals.(ABSTRACT TRUNCATED AT 250 WORDS)
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Differential development of Cholinergic Nerve terminal markers in rat brain regions: implications for Nerve terminal density, impulse activity and specific gene expression.
Brain Research, 1993Co-Authors: E.a. Zahalka, Frederic J. Seidler, S.e. Lappi, Joseph Yanai, Theodore A. SlotkinAbstract:During critical developmental periods, Cholinergic activity plays a key role in programming the development of target cells. In the current study, ontogeny of Cholinergic terminals and their activity were constrasted in 4 brain regions of the fetal and neonatal rat using choline acetyltransferase activity, which is unresponsive to changes in impulse flow, and [ 3 H]hemicholinium-3 binding, which labels the high-affinity choline transporter that upregulates in response to increased neuronal stimulation. In all 4 regions (cerebral cortex, midbrain + brainstem, striatum, hippocampus) choline acetyltransferase activity increased markedly from late gestation through young adulthood, but generally did so in parallel with the expansion of total membrane protein, reflective of axonal outgrowth and synaptic proliferation. In contrast, [ 3 H]hemicholinium-3 binding was extremely high in late gestation and immediately after birth, declined in the first postnatal week and then rose again into young adulthood. The ontogenetic changes reflected alterations primarily in the number of binding sites ( B max ) and not in binding affinity. Only the latter phas of development of [ 3 H]hemicholinium-3 binding corresponded to the ontogenetic changes in choline acetyltransferase activity; in the hippocampus, there were disparities even in young adulthood, where [ 3 H]hemicholinium-3 binding showed a spike of activity centered around the 5th to 6th postnatal week, whereas choline acetyltransferase did not. Correction of binding for membrane protein development did not eliminate any of the major differences in developmental patterns between the two markers. These results suggest that development of the choline transporter binding site is regulated independently of the outgrowth of the bulk of Cholinergic Nerve terminal. By implication, either Cholinergic Nerve impulse activity is extremely high in fetal and early neonatal stages, despite the relative sparsity of terminals, or the choline transporter labeled by [ 3 H]hemicholinium-3 is being transiently overexpressed in cells that do not possess the site in the mature nervous system.
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Dexamethasone treatment in utero enhances neonatal Cholinergic Nerve terminal development in rat brain.
Research communications in chemical pathology and pharmacology, 1993Co-Authors: E.a. Zahalka, Frederic J. Seidler, Theodore A. SlotkinAbstract:Fetal glucocorticoid administration has been proposed to elicit both promotional and inhibitory effects on neuronal development. In the current study, pregnant rats were given 0.05, 0.2 or 0.8 mg/kg of dexamethasone on gestational days 17, 18 and 19, and the effects on development of central Cholinergic projections was assessed on postnatal day 1 by measuring the specific binding of [3H]hemicholinium-3 to the high affinity choline transporter localized in Cholinergic Nerve terminal membranes. Dexamethasone produced a dose-dependent retardation of brain region growth, but enhanced [3H]hemicholinium-3 binding in both the forebrain and the midbrain + brainstem. At the highest dose, the promotional effect on [3H]hemicholinium-3 binding was lost in the forebrain, a region that is particularly sensitive during late gestation to inhibitory effects of glucocorticoids on neuronal development. These results indicate that, even in the face of growth retardation, glucocorticoids promote the development of central Cholinergic projections; however, at high doses, inhibitory actions of the steroid can offset the promotional effects in some regions.
T A Slotkin - One of the best experts on this subject based on the ideXlab platform.
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Differential development of Cholinergic Nerve terminal markers in rat brain regions: implications for Nerve terminal density, impulse activity and specific gene expression.
Brain research, 1993Co-Authors: E.a. Zahalka, S.e. Lappi, Joseph Yanai, F J Seidler, T A SlotkinAbstract:During critical developmental periods, Cholinergic activity plays a key role in programming the development of target cells. In the current study, ontogeny of Cholinergic terminals and their activity were contrasted in 4 brain regions of the fetal and neonatal rat using choline acetyltransferase activity, which is unresponsive to changes in impulse flow, and [3H]hemicholinium-3 binding, which labels the high-affinity choline transporter that upregulates in response to increased neuronal stimulation. In all 4 regions (cerebral cortex, midbrain + brainstem, striatum, hippocampus) choline acetyltransferase activity increased markedly from late gestation through young adulthood, but generally did so in parallel with the expansion of total membrane protein, reflective of axonal outgrowth and synaptic proliferation. In contrast, [3H]hemicholinium-3 binding was extremely high in late gestation and immediately after birth, declined in the first postnatal week and then rose again into young adulthood. The ontogenetic changes reflected alterations primarily in the number of binding sites (Bmax) and not in binding affinity. Only the latter phase of development of [3H]hemicholinium-3 binding corresponded to the ontogenetic changes in choline acetyltransferase activity; in the hippocampus, there were disparities even in young adulthood, where [3H]hemicholinium-3 binding showed a spike of activity centered around the 5th to 6th postnatal week, whereas choline acetyltransferase did not. Correction of binding for membrane protein development did not eliminate any of the major differences in developmental patterns between the two markers. These results suggest that development of the choline transporter binding site is regulated independently of the outgrowth of the bulk of Cholinergic Nerve terminals.(ABSTRACT TRUNCATED AT 250 WORDS)
Roy G. Goldie - One of the best experts on this subject based on the ideXlab platform.
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Influence of endothelin-1(1-31) on smooth muscle tone and Cholinergic Nerve-mediated contraction in rat isolated trachea.
Journal of Cardiovascular Pharmacology, 2000Co-Authors: Roy G. Goldie, Angela C. D'aprile, Glenn J. Self, Paul Rigby, Peter J. HenryAbstract:Endothelin-1(1-21) (ET-1(1-21)) is a strong candidate as a significant mediator in asthma, in part because of its powerful spasmogenic actions and its ability to enhance Cholinergic Nerve-mediated contraction in human and animal airway smooth muscle. In the study reported here, we have demonstrated that [125I]ET-1(1-31) binds specifically to BQ-123-sensitive sites (presumably ET(A)-receptors) and to sarafotoxin S6c (S6c)-sensitive sites (presumably ET(B)-receptors) in rat tracheal and pulmonary airways, as well as in lung alveoli. These sites coexist in tracheal airway smooth muscle and in alveolar tissue in approximately equal proportions. ET-1(1-21) and ET-1(1-31) were equipotent and approximately equally active as spasmogens in rat tracheal smooth muscle. Importantly, both peptides were shown to potentiate Cholinergic Nerve-mediated rat tracheal contraction, although ET-1(1-31) was less active in this regard. These data are consistent with the idea that ET-1(1-31) could play a significant mediator role in obstructive airway diseases such as asthma.
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Endothelin-1 potentiates Cholinergic Nerve-mediated contraction in human isolated bronchus.
The European respiratory journal, 1999Co-Authors: Lynette B. Fernandes, Peter J. Henry, Roy G. GoldieAbstract:That endothelin-1(ET-1) plays a mediator role in asthma is consistent with reports of ET-1-induced potentiation of Cholinergic Nerve-mediated contraction in airways from various animal species. This study examined the effect of ET-1 on Cholinergic contractions in human isolated bronchus. Macroscopically nondiseased human bronchial tissue was obtained from 23 patients with respiratory tumours. An electrical field stimulation (EFS) frequency that produced one third of the contraction at 30 Hz (EFS30) was estimated. The effect of ET-1 on these EFS-evoked contractions was assessed. EFS-evoked contractions were frequency-dependent and abolished by either atropine or tetrodotoxin. Thus, EFS-induced contractions were mediated by acetylcholine from Cholinergic Nerves. ET-1 (3 nM) potentiated EFS-evoked contractions by 10+/-2% EFS30 (p
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Influence of endothelin-1 on Cholinergic Nerve-mediated contractions and acetylcholine release in rat isolated tracheal smooth muscle.
Journal of Pharmacology and Experimental Therapeutics, 1996Co-Authors: P.g. Knott, Lynette Fernandes, Peter J. Henry, Roy G. GoldieAbstract:The aim of this study was to assess the influence of endothelin-1 (ET-1) on Cholinergic Nerve-mediated contractions in rat isolated tracheal smooth muscle by use of electrical-field stimulation (EFS) and \[3H]choline efflux studies. EFS (80 V, 0.5 ms, 0.1-30 Hz for 10 s) evoked transient, frequency-dependent contractions of isolated tracheal preparations. Contractions were abolished in the presence of atropine or tetrodotoxin, which suggests they were mediated by acetylcholine (ACh) release from Cholinergic Nerves. The ETB receptor-selective agonist sarafotoxin S6c (1 nM) augmented EFS (0.6-1 Hz)-induced contractions by 179%. These effects were significantly attenuated in the presence of the ETB receptor-selective antagonist N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methyl-leucyl-D-1- methoxycarbonyltryptophanyl-D-norleucine (BQ-788; 1 microM). ET-1 (1 nM) also markedly potentiated EFS-induced contractions (153%). This was apparently not a postjunctional effect, because ET-1 did not alter contractile responses to exogenously applied ACh. Cyclo[D-Trp-D-Asp-L-Pro-D-Val-L-Leu\] (BQ-123;3 microM) and BQ-788 when used alone, failed to inhibit ET-1-induced potentiation of EFS-evoked contractions. However, in their combined presence, BQ-123 and BQ-788 significantly attenuated ET-1-induced potentiation of EFS responses. EFS (100 V, 0.5 ms, 3 Hz for 2 min) applied to tracheal preparations preloaded with [3H]choline, caused airway smooth muscle contraction and an efflux of radioactivity. Both sarafotoxin S6c (10 nM) and ET-1 (10 nM) significantly enhanced the EFS-induced 3H-efflux and the latter was abolished only in the combined presence of BQ-123 and BQ-788. These data indicated that ET-1 enhances Cholinergic Nerve-mediated contractions in rat isolated trachea via activation of prejunctional ETA and ETB receptors that were linked to increased ACh release from Cholinergic Nerves.
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Potentiation by endothelin-1 of Cholinergic Nerve-mediated contractions in mouse trachea via activation of ETB receptors
British journal of pharmacology, 1995Co-Authors: Peter J. Henry, Roy G. GoldieAbstract:1. We have previously shown that endothelin-1-induced contraction of mouse isolated tracheal smooth muscle was mediated via both ETA and ETB receptors. In the current study, we have investigated endothelin-1-induced potentiation of Cholinergic Nerve-mediated contractions in mouse isolated trachea and have characterized pharmacologically the endothelin receptors mediating this response. 2. Electrical field stimulation (EFS; 70 V, 0.5 ms duration, 10s train, 0.1-60 Hz) of mouse isolated trachea caused frequency-dependent, monophasic contractions (magnitude of contraction of 60 Hz was 56 +/- 4% Cmax (n = 6), where Cmax is the contractile response to 10 microM carbachol). EFS-induced contractions were abolished by either 0.1 microM atropine or 3 microM tetrodotoxin, but were not affected by 1 microM hexamethonium, indicating that they were induced by stimulation of postganglionic Cholinergic Nerves. In contrast, contractions induced by exogenously applied acetylcholine were inhibited by atropine, but not by either tetrodotoxin or hexamethonium. 3. The ETB receptor-selective agonist, sarafotoxin S6c, caused marked concentration-dependent potentiation of EFS-induced contractions in mouse isolated tracheal segments. At 0.1 nM, sarafotoxin S6c exerted no direct contractile effect, but significantly increased a standard EFS-induced contraction of 20% Cmax by 8 +/- 2% Cmax (i.e. 1.4 fold, n = 5, P < 0.05). At higher concentrations, 10 nM sarafotoxin S6c induced a large, transient contraction (peak response of 74 +/- 2% Cmax at 10 min; 3 +/- 2% Cmax at 45 min) and enhanced the standard EFS-induced contraction by 30 +/- 4% Cmax (i.e. 2.5 fold, n = 5, P < 0.01). In contrast, 10 nM sarafotoxin S6c did not enhance contractile responses to exogenously applied acetylcholine(n = 6).4. Endothelin-1 also modulated EFS-induced contractions. At 0.1 nM, endothelin-1 exerted no direct contractile effect, but significantly increased the standard EFS-induced contraction of 20%Cmax, by 7 +/- 2%Cma, (i.e. 1.35 fold, n = 5, P
Joseph Yanai - One of the best experts on this subject based on the ideXlab platform.
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Differential development of Cholinergic Nerve terminal markers in rat brain regions: implications for Nerve terminal density, impulse activity and specific gene expression.
Brain Research, 1993Co-Authors: E.a. Zahalka, Frederic J. Seidler, S.e. Lappi, Joseph Yanai, Theodore A. SlotkinAbstract:During critical developmental periods, Cholinergic activity plays a key role in programming the development of target cells. In the current study, ontogeny of Cholinergic terminals and their activity were constrasted in 4 brain regions of the fetal and neonatal rat using choline acetyltransferase activity, which is unresponsive to changes in impulse flow, and [ 3 H]hemicholinium-3 binding, which labels the high-affinity choline transporter that upregulates in response to increased neuronal stimulation. In all 4 regions (cerebral cortex, midbrain + brainstem, striatum, hippocampus) choline acetyltransferase activity increased markedly from late gestation through young adulthood, but generally did so in parallel with the expansion of total membrane protein, reflective of axonal outgrowth and synaptic proliferation. In contrast, [ 3 H]hemicholinium-3 binding was extremely high in late gestation and immediately after birth, declined in the first postnatal week and then rose again into young adulthood. The ontogenetic changes reflected alterations primarily in the number of binding sites ( B max ) and not in binding affinity. Only the latter phas of development of [ 3 H]hemicholinium-3 binding corresponded to the ontogenetic changes in choline acetyltransferase activity; in the hippocampus, there were disparities even in young adulthood, where [ 3 H]hemicholinium-3 binding showed a spike of activity centered around the 5th to 6th postnatal week, whereas choline acetyltransferase did not. Correction of binding for membrane protein development did not eliminate any of the major differences in developmental patterns between the two markers. These results suggest that development of the choline transporter binding site is regulated independently of the outgrowth of the bulk of Cholinergic Nerve terminal. By implication, either Cholinergic Nerve impulse activity is extremely high in fetal and early neonatal stages, despite the relative sparsity of terminals, or the choline transporter labeled by [ 3 H]hemicholinium-3 is being transiently overexpressed in cells that do not possess the site in the mature nervous system.
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Differential development of Cholinergic Nerve terminal markers in rat brain regions: implications for Nerve terminal density, impulse activity and specific gene expression.
Brain research, 1993Co-Authors: E.a. Zahalka, S.e. Lappi, Joseph Yanai, F J Seidler, T A SlotkinAbstract:During critical developmental periods, Cholinergic activity plays a key role in programming the development of target cells. In the current study, ontogeny of Cholinergic terminals and their activity were contrasted in 4 brain regions of the fetal and neonatal rat using choline acetyltransferase activity, which is unresponsive to changes in impulse flow, and [3H]hemicholinium-3 binding, which labels the high-affinity choline transporter that upregulates in response to increased neuronal stimulation. In all 4 regions (cerebral cortex, midbrain + brainstem, striatum, hippocampus) choline acetyltransferase activity increased markedly from late gestation through young adulthood, but generally did so in parallel with the expansion of total membrane protein, reflective of axonal outgrowth and synaptic proliferation. In contrast, [3H]hemicholinium-3 binding was extremely high in late gestation and immediately after birth, declined in the first postnatal week and then rose again into young adulthood. The ontogenetic changes reflected alterations primarily in the number of binding sites (Bmax) and not in binding affinity. Only the latter phase of development of [3H]hemicholinium-3 binding corresponded to the ontogenetic changes in choline acetyltransferase activity; in the hippocampus, there were disparities even in young adulthood, where [3H]hemicholinium-3 binding showed a spike of activity centered around the 5th to 6th postnatal week, whereas choline acetyltransferase did not. Correction of binding for membrane protein development did not eliminate any of the major differences in developmental patterns between the two markers. These results suggest that development of the choline transporter binding site is regulated independently of the outgrowth of the bulk of Cholinergic Nerve terminals.(ABSTRACT TRUNCATED AT 250 WORDS)
S.e. Lappi - One of the best experts on this subject based on the ideXlab platform.
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Differential development of Cholinergic Nerve terminal markers in rat brain regions: implications for Nerve terminal density, impulse activity and specific gene expression.
Brain Research, 1993Co-Authors: E.a. Zahalka, Frederic J. Seidler, S.e. Lappi, Joseph Yanai, Theodore A. SlotkinAbstract:During critical developmental periods, Cholinergic activity plays a key role in programming the development of target cells. In the current study, ontogeny of Cholinergic terminals and their activity were constrasted in 4 brain regions of the fetal and neonatal rat using choline acetyltransferase activity, which is unresponsive to changes in impulse flow, and [ 3 H]hemicholinium-3 binding, which labels the high-affinity choline transporter that upregulates in response to increased neuronal stimulation. In all 4 regions (cerebral cortex, midbrain + brainstem, striatum, hippocampus) choline acetyltransferase activity increased markedly from late gestation through young adulthood, but generally did so in parallel with the expansion of total membrane protein, reflective of axonal outgrowth and synaptic proliferation. In contrast, [ 3 H]hemicholinium-3 binding was extremely high in late gestation and immediately after birth, declined in the first postnatal week and then rose again into young adulthood. The ontogenetic changes reflected alterations primarily in the number of binding sites ( B max ) and not in binding affinity. Only the latter phas of development of [ 3 H]hemicholinium-3 binding corresponded to the ontogenetic changes in choline acetyltransferase activity; in the hippocampus, there were disparities even in young adulthood, where [ 3 H]hemicholinium-3 binding showed a spike of activity centered around the 5th to 6th postnatal week, whereas choline acetyltransferase did not. Correction of binding for membrane protein development did not eliminate any of the major differences in developmental patterns between the two markers. These results suggest that development of the choline transporter binding site is regulated independently of the outgrowth of the bulk of Cholinergic Nerve terminal. By implication, either Cholinergic Nerve impulse activity is extremely high in fetal and early neonatal stages, despite the relative sparsity of terminals, or the choline transporter labeled by [ 3 H]hemicholinium-3 is being transiently overexpressed in cells that do not possess the site in the mature nervous system.
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Differential development of Cholinergic Nerve terminal markers in rat brain regions: implications for Nerve terminal density, impulse activity and specific gene expression.
Brain research, 1993Co-Authors: E.a. Zahalka, S.e. Lappi, Joseph Yanai, F J Seidler, T A SlotkinAbstract:During critical developmental periods, Cholinergic activity plays a key role in programming the development of target cells. In the current study, ontogeny of Cholinergic terminals and their activity were contrasted in 4 brain regions of the fetal and neonatal rat using choline acetyltransferase activity, which is unresponsive to changes in impulse flow, and [3H]hemicholinium-3 binding, which labels the high-affinity choline transporter that upregulates in response to increased neuronal stimulation. In all 4 regions (cerebral cortex, midbrain + brainstem, striatum, hippocampus) choline acetyltransferase activity increased markedly from late gestation through young adulthood, but generally did so in parallel with the expansion of total membrane protein, reflective of axonal outgrowth and synaptic proliferation. In contrast, [3H]hemicholinium-3 binding was extremely high in late gestation and immediately after birth, declined in the first postnatal week and then rose again into young adulthood. The ontogenetic changes reflected alterations primarily in the number of binding sites (Bmax) and not in binding affinity. Only the latter phase of development of [3H]hemicholinium-3 binding corresponded to the ontogenetic changes in choline acetyltransferase activity; in the hippocampus, there were disparities even in young adulthood, where [3H]hemicholinium-3 binding showed a spike of activity centered around the 5th to 6th postnatal week, whereas choline acetyltransferase did not. Correction of binding for membrane protein development did not eliminate any of the major differences in developmental patterns between the two markers. These results suggest that development of the choline transporter binding site is regulated independently of the outgrowth of the bulk of Cholinergic Nerve terminals.(ABSTRACT TRUNCATED AT 250 WORDS)