摘要:

AbstractResults obtained previously indicate that the firing pattern of midbrain dopamine (DA) neurons is of importance for the terminal DA release. In the present combined electrophysiological and microdialysis study, the influence of the firing pattern on striatal DA release was studied by using the previously observed ability of low doses of β‐hydroxybutyrate (GHBA) to profoundly regularise the firing pattern of rat DA neurons in the substantia nigra (SN). Administration of GHBA (200 mg/kg, i.v.) did not significantly reduce the firing rate of any of the DA neurons recorded from, but rather caused a slight transient excitation. However, this dose of the drug caused a profound regularisation of the firing pattern and abolished burst activity of the DA neurons. The DA concentration in the dialysate obtained from the striatum (10 min sampling periods) decreased with the lowest value (67% of predrug value) observed at the sampling period 20‐30 min after the GHBA administration. As a complement to microdialysis, the 3‐methoxytyramine (3‐MT) accumulation in striatal tissue following monoamine oxidase inhibition was determined as an indirect measure of DA release in vivo. The 3‐MT concentrations in the striatum decreased to 84% of controls following 200 mg/kg of GHBA. To exclude an effect on DA release conceivably mediated by GHBA locally in the striatum, GHBA (10−7‐10−3M) was given locally in the dialysis probe and was found to increase DA in the dialysate (maximally to 140% of controls). The present results are in line with previous electrophysiological studies which have demonstrated that artificially induced burst firing by electrical stimulation is associated with an increased extracellular level of striatal DA (as determined by in vivo voltammetric techniques or microdialysis) and support the idea that firing pattern may be an important physiological modulatory mechanism for the release of terminal neurotransmitter. © 199

ISSN:0887-4476    

DOI:10.1002/syn.890170402

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe insulin‐like growth factor (IGF) signaling system includes the growth factors and their cell surface receptors, along with circulating IGF binding proteins (IGFBPs) that may alter and modulate the action of these neurotrophic hormones. These IGFBPs, along with IGFs and receptors, have been detected in various tissues including the brain. In this study, using polyclonal antibody to human IGFBP‐1 or bovine IGFBP‐2, we found that mouse muscle extracts contain similar‐sized proteins that crossreact with these antibodies on Western immunoblots. After establishing that these antibodies reacted with the homologous murine IGFBPs, we performed immunocytochemistry to demonstrate the localization of IGFBP‐1 at the neuromuscular junction, a model nicotinic, cholinergic synapse, as well as within intramuscular nerves. IGFBP‐2, a distinct macromolecule, is present on the surface of muscle fibers and is not present within synapses or nerves. © 1994 Wil

ISSN:0887-4476    

DOI:10.1002/syn.890170403

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractDopamine neurons derived from the mesencephalon of embryonic rats were maintained in primary culture, identified and studied with whole‐cell patch recording techniques. These neurons demonstrated a rapidly activating and inactivating voltage‐dependent outward current which required the presence of K+ions. This current was termed IAbecause of its transient nature. It was elicited by step depolarizations from holding potentials more negative than ‐50 mV and exhibited steady‐state inactivation at a membrane potential more positive than ‐40 mV and half‐maximal inactivation observed at ‐65 mV. This current rapidly achieved peak activation in less than 8 msec and decayed with a time constant (τ) of 58±5 msec. This current was observed in the presence of tetraethylammonium but was readily blocked by 4‐aminopyridine (2‐4 mM). This current was also observed to be modulated by stimulation of D2dopamine receptors (DA autoreceptors) located on the dopamine neurons. Thus, both DA and the D2receptor agonist quinpirole enhanced the peak IAobserved, while the partial D1receptor agonist SKF 38393 was without effect. The enhancement of IAwas confirmed to be due to the activation of D2 receptors as the effects of either DA or quinpirole were blocked by the D2receptor antagonists eticlopride and sulpiride, but not by the D1receptor antagonist SCH 23390. Since we have previously demonstrated that the IKpresent: in these cells is also enhanced by D2receptor stimulation, we investigated the signal transduction pathways involved in coupling DA autoreceptors to both IAand IK. The response of both these potassium currents to DA autoreceptor stimulation was completely abolished by the preincubation of cultures with pertussis toxin, indicating the possible involvement of the G proteins Giand GO. In an attempt to further characterize which G protein may be involved, additional experiments were performed. The ability of DA autoreceptor stimulation to augment both currents was also blocked completely when G protein activation was prevented by the intracellular application of GDPßS (100 μM). In contrast, irreversible activation of G proteins by intracellular application of the nonhydrolyzable GTP analog GTPγS (100 μM) mimicked the effects of DA autoreceptor stimulation on both IAand IK. In addition, the intracellular application of a polyclonal antibody that was selective for the β‐subunit of GOcompletely abolished the DA autoreceptor modulation of both currents while preimmune serum was without effect. Taken together, these data demonstrate that the enhancement of IAand IKin response to stimulation of DA autoreceptors is dependent upon the activation of GOand appears to involve a GOαsubu

ISSN:0887-4476    

DOI:10.1002/syn.890170404

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractIn order to further characterize the pharmacologic mechanisms that mediate the antipsychotic drug‐induced increase in neurotensin (NT) in nucleus accumbens and striatum, the effects of three weeks treatment with psychotherapeutic levels of lithium alone or in conjunction with haloperidol were compared to the ability of haloperidol alone to alter NT and neuromedin N (NMN) regional brain concentrations in rats. A separate experiment examined the ability of a selective dopamine D2 receptor agonist, quinelorane, to alter NT/NMN regional concentrations after three weeks of treatment as compared to haloperidol, a D2receptor antagonist. Haloperidol (1 mg/kg) increased both NT and NMN concentrations in several brain regions and these parallel peptide increases were highly correlated. Lithium chloride (0.4 mM) had no effect, either alone or with haloperidol, on NT/NMN concentrations. Quinelorane (1 mg/kg), however, effectively increased both NT and NMN concentrations in the caudate nucleus and nucleus accumbens, as did haloperidol (2 mg/kg). These data indicate that the induction of NT and NMN, whose adjacent sequences are contained in a pro‐hormone product of a single gene, occurs in tandem and remains proportional, as well as demonstrating that putative D2receptor agonists can produce effects on NT/NMN systems that are similar to D2receptor antagonists. © 1994 Wiley‐Lis

ISSN:0887-4476    

DOI:10.1002/syn.890170405

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractDendritic spines are generally believed to play a role in modulating synaptically induced electrical events. In addition, they may also confine second messengers and thus topologically limit the distance over which second messenger cascades may be functionally significant. In order to address this possibility, computer simulations of transient second messenger concentration changes were performed. The results show the importance of spine morphology and binding and extrusion mechanisms in controlling second messenger transients. In the presence of intrinsic cytoplasmic binding sites and kinetic rates similar to that expected for calcium, second messengers were confined to the spine head. In the absence of binding/extrusion mechanisms, the size and time course of the input transient to the spine head influenced the second messenger transients that might be seen at the base of the spine neck and in other spines. Large and/or sustained increases in second messenger concentration in the spine head were communicated to the spine base and to other spine heads. The results emphasize the importance of a knowledge of breakdown pathways, concentrations and kinetics of binding sites, and extrusion mechanisms for understanding the dynamics of local chemical changes for dendritic spine function. © 1994 Wiley‐Liss, I

ISSN:0887-4476    

DOI:10.1002/syn.890170406

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractIn a previous report, we described the ability of two secretogogues, histamine and nicotine, to stimulate additive effects on catecholamine (CA) release and synapsin II phosphorylation in bovine adrenal chromaffin cells (BACC) [Firestone and Browning (1992), J. Neurochem., 58:441–447]. We hypothesized that these results were due to the combined effects on cytosolic Ca++of the two distinct signalling pathways. We therefore examined the intracellular Ca++signals stimulated by histamine and nicotine, alone and together. In Ca++‐deficient medium, nicotine‐stimulated signals were abolished, whereas histamine‐stimulated signals were maintained, demonstrating that nicotine depended entirely on Ca++influx for its effects. Indeed, the nicotine‐stimulated signal could also be prevented using a Ca++channel blocker, nicardipine. Further, the observation that exposure of BACC to thapsigargin reduced histamine‐stimulated Ca++signals verified that histamine mobilizes Ca++from intracellular stores. Thus, the two secretogogues mobilize Ca++from distinct pools. When BACC were stimulated with the two secretogogues together, the resulting Ca++signal was greater than that from either alone. These data are consistent with a model in which two distinct sources of Ca++can summate within the cell, producing a greater Ca++signal and, hence, a greater effect on neurotransmitter release. © 1994 Wil

ISSN:0887-4476    

DOI:10.1002/syn.890170407

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890170408

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890170409

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890170401

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY