bluuebunny/crossref_metadata_2025_split huggingface dataset:
Norepinephrine uptake dependent upon apparent Mg++‐ATPase activity and proton transport in storage vesicles in axoplasm
Authors: Bogdanski D. F. 
Published: January 2005

AbstractA Ca++‐dependent secretion of norepinephrine ([3H]NE) was evoked in adrenergic nerve endings in rat heart ventricle slices incubated in a modified KrebsHCO3 medium containing choline C1 as the replacement for NaC1 (Ch+‐Ca++). Exogenous ATP inhibited secretion and lithium ion, a known inhibitor of NE uptake dependent upon Mg++‐ATPase activity in vesicles (but not ouabain) prevented the response to ATP (Bogdanski, 1983, 1986). It was suggested that vesicles attached to the axolemma recaptured[3H]NE from the extracellular fluid. This report indicates that other known inhibitors of uptake in isolated vesicles also inhibited the response to ATP in the attached vesicles. Included were two inhibitors of Mg++‐ATPase activity, N‐ethylmaleimide (NEM) and dicyclohexylcarbodiimide (DCCD), and the proton transporters 2,4‐dinitrophenol (2,4‐ DNP 1.0 mM) and chlorpromazine (CPZ). Potassium ionophores (valinomycin with 2,4‐DNP 0.1 mM and, nigericin) and a pH neutralizing reagent for vesicles (NH3 from ammonium sulfate in solution) were also effective. The uptake inhibitors, except 2,4‐DNP, could also increase the rate of depletion of stored NE and its deamination in nonsecreting nerve endings incubated in Krebs‐HCO3 (KRB) medium. Valinomycin by itself stimulated uptake in the presence of ATP. It is sugested that mechanisms of uptake and retention of NE in isolated vesicles (symposium (1982) Fed. Proc. 41:2742–2780) apply to the axoplasmic vesicles as well. Thus, the activity of Mg++‐ATPase drives proton transport to establish the electrochemical gradients of H+, which drive the transport of NE. A lowering of the gradients can mobilize amines and evoke secretion. However, isolated vesicles in the presence of ATP and C1− eventually take up a sufficient number of ions to cause osmotic lysis. By contrast, exocytosis was not biochemically apparent in the model vesicular‐axolemmal secretory and transmitter recovery unit.
Substance P‐mediated membrane currents in voltage‐clamped guinea pig inferior mesenteric ganglion cells
Authors: Griffith William H. , Hills Judith M. , Brown David A. 
Published: January 2005

AbstractResponses to substance P (SP) and to hypogastric nerve stimulation were recorded from voltage‐clamped guinea pig inferior mesenteric ganglion (IMG) neurons, and compared with those to muscarine. Muscarine produced a voltage‐dependent inward current accompanied by a reduced input conductance and inhibition of IM a time‐ and voltage‐dependent K+‐current (Brown and Adams: Nature 283:673–676, 1980). SP also produced an inward current, accompanied by a fall in input conductance (20 out of 31 cells) or a rise in input conductance (7 out of 31 cells). The fall in input conductance was not accompanied by an inhibition of M‐current (unlike frog ganglia: Adams et al.: British Journal of Pharmacology 79:330–333, 1983) or an inhibition of the inward rectifier current (unlike globus pallidus neurons: Stanfield et al.: Nature 315:498–501, 1985). Repetitive hypogastric nerve stimulation (10–20 Hz, 2–10 s) produced a slow inward postsynaptic current lasting 1–3 min, with decreases or increases of input conductance matching those produced by SP. The postsynaptic current did not show a consistent or reproducible change in amplitude on varying the holding potential between ‐90 and ‐25 mV. It is concluded that SP and hypogastric stimulation produce complex and variable changes in ionic conductance in IMG neurons.
A1 Noradrenergic action on medial preoptic‐medial septal neurons: A neuropharmacological study
Authors: Kim Yang I. , Dudley Carol A. , Moss Robert L. 
Published: January 2005

AbstractIn an attempt to determine whether the excitatory and inhibitory orthodromic responses of single medial preoptic‐medial septal (MPO‐S) neurons to discrete electrical stimulation of the A1 noradrenergic region were mediated specifically by norepinephrine (NE) and involved different types of adrenoreceptors, a series of electrophysiological and neuropharmacological experiments was conducted. Extracellular single unit recording and local drug application techniques were used in female rats under urethane anesthesia. Chemical lesion of the catecholaminergic nerve terminal plexus in the medial preoptic area with 6‐hydroxydopamine abolished both excitatory and inhibitory orthodromic effects of A1 region stimulation on MPO‐S neurons, suggesting the noradrenergic nature of the effects. This conclusion was corroborated by the observation that the orthodromic effects were mimicked by locally applied exogenous NE. The excitatory effects were reliably mimicked by a low concentration of NE (0.5 mM; in‐barrel concentration) and methoxamine (1.0 mM, an alpha‐1 agonist), but not by either low or high concentration (1 and 100 mM) of clonidine (an alpha‐2 agonist) and isoproterenol (a beta agonist). The inhibitory orthodromic effects of A1 region stimulation were reliably mimicked by a high concentration of NE (50 mM), clonidine (100 mM) and isoproterenol (100 mM), but not by a low concentration of NE (0.5 mM), methoxamine (1mM), clonidine (1 mM) or isoproterenol (1 mM). A high concentration (100 mM) of methoxamine mimicked the inhibitory effects less than 40% of the time. The low concentration (0.5 mM) NE‐induced excitation that matched the excitatory orthodromic effect of A1 region stimulation was blocked by phentolamine (100 mM), an alpha blocker, but not by timolol (100 mM), a beta blocker. On the other hand, the high concentration (50 mM) NE‐induced inhibition that matched the inhibitory orthodromic effect of A1 region stimulation was blocked by timolol, but not by phentolamine.Taken together, the present results are consistent with the hypothese that the ascending noradrenergic projections from the A1 region affect the excitability of MPO‐S neurons directly through NE and that the excitatory and inhibitory orthodromic effects involve different types of adrenoreceptors, i.e., alpha‐1 and beta receptors, respectively.
Organization of dopamine D1 and D2 receptors in human striatum: Receptor autoradiographic studies in Huntington's disease and schizophrenia
Authors: Joyce Jeffrey N. , Lexow Nedra , Bird Edward , Winokur Andrew 
Published: January 2005

AbstractThe technique of quantitative autoradiography was used to examine the effects of Huntington's disease (HD) and schizophrenia on the organization of striatal dopamine (DA) D1 and D2 receptors. Whereas the striatum of HD cases showed a reduction in the density of D1 ([3H]SCH 23390) and D2 ([3H]spiroperidol) receptors, the patterning of D2 receptor loss did not match that of the D1 receptor loss. The HD loss of D1 D1 receptors (65%) is far greater than the loss of D2 receptors (28%). Whereas there was a dorsal‐ventral gradient of effect on both receptor subtypes, the effects of HD on D2 receptors in the ventral putamen (PUT) and nucleus accumben septi (NAS) were minimal. Similarly, muscarinic M1 and M2 receptors demonstrate different patterns of alteration in HD. The M2 subtype, labeled with [3H]N‐methylscopolamine (in the presence of excess pirenzepine to occlude M1 sites), was depleted far more than the M1 receptor subtype, labeled with [3H]pirenzepine. Although the effects of HD on [3H]mazindol labeling of DA terminals were more heterogeneous, there appeared to be a relative preservation of this afferent input to the striatum of the HD cases. In the schizophrenic cases, our autoradiographic studies confirm previous reports of an elevation of D2 receptor density in the striata of many schizophrenics. This increase was evident even though two of the three cases were known to have not been treated with neuroleptics, and the third case may also have been drug naive. however, the increase was far greater in the NAS (164%) and ventral PUT (173%) than more dorsally in the striatum (68%). The density of D1 receptors and DA terminals labeled with [3H]mazindol in the striatum of schizophrenics was not significantly different from that of control cases. Thus in both HD and schizophrenia, the ratio of D2/D1 receptors is altered in favor of the D2 population, particularly in the NAS.
Norepinephrine stimulation of adenylate cyclase potentiates protein kinase C action: Electrophysiological studies in the dentate gyrus
Authors: Stratton Kathleen R. , Baraban Jay M. , Worley Paul F. 
Published: January 2005

AbstractProtein kinase C and norepinephrine‐stimulated adenylate cyclase have been linked to formation of long‐term potentiation in the dentate gyrus. However, little is known about second messenger system interactions regulating synaptic transmission. In electrophysiological studies of the dentate gyrus, we observe synergistic interactions between norepinephrine and phorbol esters, activators of protein kinase C. Norepinephrine markedly potentiates the block of adenosine's inhibitory action by phorbol esters. Norepinephrine's action is mimicked by the β‐adrenoceptor agonist isoproterenol and blocked by the β‐adrenoceptor antagonists timolol and propranolol. Forskolin also mimicks norepinephrine's action. Accordingly, norepinephrine's potentiation of protein kinase C appears to be mediated by the cyclic AMP second messenger system. This mechanism may contribute to norepinephrine's facilitation of long‐term potentiation in the dentate gyrus.
Reciprocal zones of excitation and inhibition in the neostriatum
Authors: Rebec George V. , D. Curtis Stephen 
Published: January 2005

AbstractSingle‐unit activity was recorded in the rat neostriatum at different distances from the point of an infusion of either glutamate or serotonin. In each case, firing rate at the distant site (0.8–1.5 mm) was the mirror image of that at the near site (0.1–0.3 mm). These reciprocal changes were blocked by a subsequent injection of haloperidol, a dopamine antagonist. It appears that a lateral inhibitory network, intrinsic to the neostriatum and possibly modulated by dopamine, plays an important role in the operation of the neostriatum.
Cocaine: An in vivo microdialysis evaluation of its acute action on dopamine transmission in rat striatum
Authors: Hurd Yasmin L. , Ungerstedt Urban 
Published: January 2005

AbstractThe effects of cocaine on dopamine (DA) neurotransmission were evaluated by in vivo microdialysis in the striatum of halothane‐anesthetized rats. Intravenous cocaine produced a dose‐dependent, transient increase of the extracellular concentration of DA, with a peak response within 10 min and a return to control level by 30 min. The sharp DA response pattern was abolished in a calcium‐free environment, indicating that DA release enhanced by cocaine originates from a vesicular storage pool. Continuous administration of cocaine (via the perfusion medium) directly into the nigrostriatal terminal region also produced a dose‐dependent increase in DA release. Low concentrations (10−5 M and 10−6 M) of cocaine maintained DA at a constant stable level, consistent with the effects observed after potent DA uptake inhibitory agents (e.g., nomifensine and Lu19005). However, continuous exposure to high concentrations (< 10−4 M) induced a transient elevation of DA within 20 min, following which DA decreased to a stable but high level; this decrease might reflect tolerance to the effect of cocaine. Administration of cocaine (10−3 M) into the substantia nigra did not change striatal DA release. The local striatal action of cocaine was less potent than amphetamine in elevating DA overflow and in its effect on DA metabolism. These findings suggest that the fast transient enhancement of DA by intravenous cocaine is most likely a consequence of the transient presence of cocaine in the terminal region, correlating with the well‐known rapid pharmacokinetic and behavioral aspects of the drug.
Cocaine alters opiate receptor binding in critical brain reward regions
Authors: Hammer Ronald P. 
Published: January 2005

AbstractBrain reward systems are thought to be involved in the reinforcing effect of both cocaine and opiates. In vitro receptor autoradiography was used to determine the effect of chronic, continuous cocaine exposure of 2 weeks duration on [3H]naloxone binding in various regions of rat brain. Although cocaine action in the central nervous system is usually associated with altered dopamine function, we observed that opiate receptor density as labeled by [3H]naloxone was altered by chronic cocaine exposure in critical brain reward regions, including the nucleus accumbens, ventral pallidum, and lateral hypothalamus. Endogenous opioid activity at opiate receptors in these critical regions may be associated with the reinforcement induced by both cocaine and opiates.
Rate‐limiting step for transmission at excitatory synapses in hippocampus
Authors: Muller Dominique , Lynch Gary 
Published: January 2005

AbstractTo examine mechanisms that might be responsible for limiting transmission at excitatory synapses in hippocampus, we analyzed the relationship between extracellular calcium concentrations (1‐6 mM) and postsynaptic responses in field CA1 of hippocampal slices using low stimulation intensities and a paired‐pulse paradigm. Three effects were observedOne, the relationship between calcium levels and the slope (or amplitude) of the postsynaptic response was described by a sigmoidal function with an asymptote at about 4 mM. Double reciprocal pilots relating calcium concentration to the initial slope of EPSPs provided evidence for the cooperativity expected between calcium ions and transmitter release.Two, both the rise time and half‐decay time of the postsynaptic responses were reduced with increasing calcium concentrations. These effects of calcium were more pronounced on the first response elicited by paired‐pulse stimulation and were considerably attenuated by 2 μM bicuculline, indicating that feed‐forward inhibition was positively related to calcium concentration and differentially activated by repetitive stimulation. However, inhibition was not responsible for the asymptotic relationship observed between calcium and response size.Three, while increasing the calcium concentration beyond 4 mM did not further affect the initial slope of excitatory postsynaptic potentials (EPSPs), paired‐pulse facilitation and 4‐aminopyridine were still effective in increasing response size. These results suggest (1)that neither the number of postsynaptic receptors nor the number of transmitter quanta available for release were limiting transmission as a function of the calcium concentration; and (2)that calcium entry into presynaptic terminals was likely to represent the limiting step under the conditions used.
Cholinergic modulation of frequency receptive fields in auditory cortex: II. Frequency‐specific effects of anticholinesterases provide evidence for a modulatory action of endogenous Ach
Authors: Ashe John H. , McKenna Thomas M. , Weinberger Norman M. 
Published: January 2005

AbstractExogenously applied muscarinic agonists—for example, acetylcholine (ACh) and acetyl‐beta‐methacholine (MCh)—modify frequency receptive fields in auditory cortex of unanesthetized animals in a frequency‐specific rather than global manner. The present study sought to relate these findings to endogenous actions of ACh by using the anticholinesterase agents eserine sulphate and soman (0‐1,2,2‐trimethylpropylmethylphosphonofluoridate) to facilitate the effects of endogenous ACh. Frequency receptive fields (FRF) were determined by presenting sequences of different isointensity tones before, during, and after application of ACh, MCh, eserine, or soman; also the cholinesterase blockers were applied between applications of ACh or MCh. The major effects produced by the inhibitors were similar to those of the agonists. Predominant effects were frequency‐specific changes in FRF. Further, eserine and soman, similar to ACh and MCh, produced shifts in the best frequency (BF) of FRF due mainly to coordinated depression of responses to the BF and increased responses to adjacent, non‐BF. The results indicate that exogenous and endogenous ACh, acting via muscarinic receptors, can significantly influence the physiological functioning of cortical neurons and consequently their processing of sensory information.
Ultrastructural description of taurine‐like immunoreactive cells and processes in the rat hippocampus
Authors: Clements Jane Reichert , Magnusson Kathy Ruth , Beitz Alvin James 
Published: January 2005

AbstractA monoclonal antibody against taurine conjugated to KLH was used to identify and describe taurine‐like immunoreactive processes in the rat hippocampus. Tissue from perfused rats was processed for immunohistochemical visualization of taurine and embedded for electron microscopy. Representative tissue samples from three regions, the dentate gyrus, CA3, and CA1, were sectioned, examined, and photographed. In the dentate gyrus, both granule cells and pyramidal basket cells were taurine‐like immunoreactive. Some axon terminals in the dentate gyrus molecular layer as well as some mossy fiber boutons in the hilus were also taurine‐like immunoreactive. In the CA3 region both pyramidal neurons and glial cells were taurine‐like immunoreactive. A few small‐diameter axon terminals in stratum radiatum and some mossy fiber boutons in stratum lucidum were taurine‐like immunoreactive. In CA1, pyramidal neurons and some glia were intensely taurine‐like immunoreactive. A few immunoreactive axon terminals were seen in stratum radiatum and stratum oriens. In all regions, dendritic staining predominated. Our results support the hypothesis that while taurine may act as a neurotransmitter in a small portion of hippocampal terminals, its main function is probably as a neuromodulator or ionic regulator.
Differential effect of cocaine on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens: Comparison to amphetamine
Authors: Moghaddam Bita , Bunney Benhamin S. 
Published: January 2005

AbstractThe technique of in vivo microdialysis was used to measure the extracellular levels of dopamine in the nucleus accumbens septi and medial prefrontal cortex of chloral‐hydrate‐anaesthetized rats following systemic administration of cocaine and amphetamine. Intravenous injection of cocaine increased the extracellular levels of dopamine in the medial prefrontal cortex and the nucleus accumbens septi in a dose‐dependent manner. However, the magnitude of increase was significantly greater in nucleus accumbens than in medial prefrontal cortex. In comparison to cocaine, amphetamine increased the extracellular levels of dopamine in the nucleus accumbens and medial prefrontal cortex to the same degree. Based on the relatively small increase of extracellular dopamine levels in medial prefrontal cortex by cocaine, it is postulated that dopaminergic innervation of other structures besides medial prefrontal cortex may be involved in maintenance of cocaine self‐administration.
Synaptic modulation of N‐methyl‐D‐asparatate receptor mediated responses in hippocampus
Authors: Muller Dominique , Lynch Gary 
Published: January 2005

AbstractLow magnesium medium and the N‐methyl‐D‐aspartate (NMDA) receptor antagonist D‐2‐amino‐5‐phosphonopentanoate (D‐AP5) were used to analyze the effect of several manipulations on the component of excitatory postsynaptic potentials (EPSPs) mediateed by activation of NDMA receptors in area CA1 of hippocampal slices. The D‐AP5 sensitive component of synaptic response was characterized by a marked sensitivity to changes in extracellular magnesium and calcium concentrations. In both cases the changes in D‐AP5 sensitive responses were considerably larger than those in non‐NMDA‐dependent potentials. Similarly, frequency facilitation, which is due to a transient increase in release, was accompanied by a greater enhancement of NMDA than non‐NMDA receptor‐mediated components. The degree of paired‐pulse facilitation observed with D‐AP5 sensitive responses was magnesium‐dependent between, concentrations of 0.05 and 0.5 mM, an effect not seen with control potentials. Intracellular injections of hyperpolarizing current pulses differentially affected NMDA and non‐NMDA receptor‐mediated components. Taken together, these results indicate that changes in the amount of transmitter release may affect to agreater degree NMDA than non‐NMDA receptor‐mediated components of synaptic responses, probably because of the voltage‐sensitive blockade by magnesium of the NMDA receptors. In contrast, induction of long‐term potentiation (LTP) by high frequency stimulation produced a larger increase in non‐NMDA as opposed to NMDA receptor‐dependent responses, a result that does not support the idea that an increases in transmitter release is responsible for LTP.
αAl2‐Adrenoceptors mediate the inhibition of cholinergic transmission in parasympathetic ganglia of the rabbit urinary bladder
Authors: Tsurusaki Masashi , Yoshida Masami , Akasu Takashi , Nagatsu Ikuko 
Published: January 2005

AbstractIntracellualar recordings were made from neurons of vesical parasympathetic ganglia (VPG) isolated from the rabbit urinary bladder and maintained, in vitro. Bath‐application of norepinephrine (NE, 500 mM–5 m̈M) caused a hyperpolarizing response at the postsynaptic membrane of VPG neurons in a concentration‐dependent manner. NE blocked the action potential elicited by an orthodromic stimulation of preganglionic (pelvic) nerve fibers. AT a relatively low concentration (5–100 nM), NE depressed the fast excitatory postsynaptic potential (EPSP), without producing the hyperpolarization. NE (100 nM) produced 49 ± 17% (N=5) decrease in the amplitude of the fast EPSP. NE did not depress the acetylcholine (ACh) potential produced by iontophoretic application of ACh to the ganglion cells. NE did not affect the amplitude of the miniature EPSP, while it reduced the frequency of miniature EPSPs. These results suggest that NE inhibits the nicotinic transmission in the rabbit VPG, probably reducing theh ACh release from presynaptic nerve terminals. Epinephrine (1 m̈M) was more potent than NE (1 m̈M) in producing the hyperpolarization as well as the blockade of the fast EPSP amplitude. Isoproterenol was ineffective as an agonist for these inhibitory adrenoceptors. Clonidine mimicked the effect of NE on the fast EPSP. Yohimbine and idazoxan antagonized both the inhibition of the fast EPSP and the hyperpolarization produced by NE. These results suggest that α2‐adrenoceptors are responsible for the inhibition of the neuronal activity in parasympathetic ganglia of the rabbit urinary bladder. Immunohistochemical study demonstrated the presence of tyrosine hydroxylase (TH)‐labelled neuronal elements in the VPG. They were a small proportion of principal neurons, their dendrites, and many varicose fibers. TH‐labelled varicosities were often situated in close proximity to the unlabelled principal neurons. TH‐labelled small cells also formed clusters among the principal neurons of VPG.
Presynaptic calcium currents evoking quantal transmission from avian ciliary ganglion neurons
Authors: Brosius D. C. , Hackett J. T. , Tuttle J. B. 
Published: January 2005

AbstractUsing whole‐cell patch clamp techniques, we simultaneously recorded presynaptic Ca++ current and excitatory postsynaptic currents (EPSCs) from avian neuromuscular junctions in culture. Quantal synaptic transmission was proportional to evoked presynaptic Ca++ current except with large stimuli, which evoked brusts of quanta, reflecting a shift to synchronized release. Synaptic delay, measured from the onset of presynaptic depolarization to the appearnce of the first postsynaptic quantal response, was often greater than 100 msec for weak depolarizations but declined as stimulus intensity was increased. Quantal events evoked by Ca++ tail currents had a mean synaptic delay of 1.67 msec. The single type of presynaptic Ca++ current observed displayed an inactivation time constant of > 100 msec and tail currents well fit by a single exponential function.