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1.
Abstract: [3 H]Strychnine specifically binds to membrane fractions isolated from rat retinae. The binding is saturable, with an apparent dissociation constant, K D , of 14.3 × 10−9 M and 205 fmol bound/mg protein. Specific binding is time-dependent and proportional to protein concentration. Glycine and taurine are equally potent inhibitors of [3 H]strychnine binding ( K i = 4 × 10−5 M); no other amino acids endogenously present in the retina inhibited [3 H]strychnine binding. 相似文献
2.
S. F. Muakkassah-Kelly J. W. Andresen J. C. Shih P. Hochstein 《Journal of neurochemistry》1983,41(5):1429-1438
Abstract: Ascorbate-induced lipid peroxidation, as measured by malonyldialdehyde (MDA) production, caused irreversible decreases in Bmax of both [3 H]5-HT and [3 H]spiperone binding. Cacl2 (4mM) inhibited ascorbateinduced MDA formation at ascorbate concentrations >0.57 mM, but not at ≤ 0.57 mM. Under the standard assay conditions (5.7 mM ascorbate and 4mM CaCl2 ), Cacl2 inhibited the MDA production casued by ascorbate by 88%, and the loss in [3 H]5-HT binding by 57%. Ascorbate still decreased [3 H]5-HT binding by 57%. Ascorbate still decreased [3 H]5-HT binding when lipid peroxidation was completely inhibited by EDTA. This additional effect of ascorbate was reversible after washing the membranes. Other reducing agents (dithiothreitol, glutathione, and metabisulfite) also decreased the binding of [3 H]serotonin. In contrast, [3 H]spiperone binding was not affected by ascorbate in the absence of lipid peroxidation or by other reducing agents. These experiments demonstrate that ascorbate has a dual and differential effect on serotonin binding sites. First, ascorbate-induced lipid peroxiation irreversibly inactivates both [3 H]5-HT and [3 H]spiperone binding. Second, independent of lipid peroxidation, there is a direct, reversible effect of ascorbate on [3 H]serotonin but not on [3 H]spiperone binding, which is probably due to the difference in the biochemical nature of the two serotonin binding sites. 相似文献
3.
B. Kenneth Koe Lorraine A. Lebel Carol B. Fox John E. Macor 《Journal of neurochemistry》1992,58(4):1268-1276
Abstract: 3-(1,2,5,6-Tetrahydro-4-pyridyl)-5- n -propoxyindole (CP-96,501) was found to be a more selective ligand at the serotonin 5-HT1B receptor than the commonly used 5-HT1B agonist, 3-(1,2,5,6-tetrahydro-4-pyridyl)-5-methoxyindole (RU 24969). In rat brain membranes, the tritiated derivative, [3 H]CP-96,501, was found to bind with a high affinity ( K D , 0.21 n M ) to a single binding site ( n H , 1.0). The receptor density of this site ( B max , 72 fmol/mg of protein) matched that of the 5-HT1B receptor determined with [3 H]5-HT. Competition curves of 16 serotonergic compounds in [3 H]CP-96,501 binding also indicated a single binding site. The rank order of their binding affinities with this new radioligand showed a high degree of correlation with their affinities at the 5-HT1B receptor determined with [3 H]5-HT or [125 I]iodocyanopindolol. Serotonergic compounds displayed competitive inhibition of [3 H]CP-96,501 binding. In the presence of 5'-guanylylimidodiphosphate [Gpp(NH)p], [3 H]CP-96,501 binding was reduced, while the potency of CP-96,501 to displace [125 I]iodocyanopindolol binding was also decreased. These findings are consistent with the agonist nature of CP-96,501. The results of this study suggest that [3 H]CP-96,501 is a useful agonist radioligand for the 5-HT1B receptor. 相似文献
4.
Douglas W. Bonhaus Eric Stefanich Dana N. Loury Sherry A. O. Hsu Richard M. Eglen Erik H. F. Wong 《Journal of neurochemistry》1995,65(1):104-110
Abstract: Cooperation in the action of agonists suggests that there are multiple binding sites on 5-hydroxytryptamine3 (5-HT3 ) receptors. The purpose of this study was to characterize these binding sites and their interactions on both native and cloned 5-HT3 receptors. The affinities of competitive 5-HT3 receptor antagonists were similar regardless of whether the receptors were labeled with [3 H]RS-42358, [3 H]granisetron, or 1-( m -[3 H]chlorophenyl)biguanide ([3 H]mCPG). By contrast, the affinities of the agonists 5-HT, mCPG, and phenylbiguanide were approximately 10-fold higher when the receptors were labeled with [3 H]mCPG. The dissociation of [3 H]mCPG, [3 H]RS-42358, and [3 H]RS-25259, but not [3 H]granisetron, from both cloned and native 5-HT3 receptors was markedly slower in the presence of 5-HT or 2-methyl-5-HT than in the presence of antagonists such as RS-42358. This suggests that the binding of these agonists to unoccupied sites on the receptor can increase the receptor's affinity for prebound ligands and thereby slow their dissociation. These data support previous indications of positive cooperation among multiple binding sites on both native and cloned 5-HT3 receptors, and they extend this idea by demonstrating that agonists can modify the interaction of some, but not all, antagonists with the receptor. 相似文献
5.
Carme Solà Emili Martínez Lluïsa Camón Angel Pazos† Eduard Rodríguez-Farré 《Journal of neurochemistry》1993,60(5):1821-1834
Abstract: The effect of lindane administration on the specific binding of ligands to different sites on the GABAA receptor-ionophore complex was studied in the rat brain by receptor mapping autoradiography. [3 H]Muscimol (Mus), [3 H]flunitrazepam (Flu), and t -[35 S]butylbicyclophosphorothionate (TBPS) were used as specific ligands of GABA, benzodiazepine, and picrotoxinin binding sites, respectively. Rats received a single oral dose of 30 mg/kg lindane and they were classified into two groups according to the absence or presence of convulsions. Vehicle-treated groups acted as controls. The effect of the xenobiotic on ligand binding was measured in different brain areas and nuclei 12 min or 5 h after its administration. Lindane induced a generalized decrease in [35 S]TBPS binding, which was present shortly after dosing. In addition, [3 H]Flu binding was increased in lindane-treated animals, this modification also appearing shortly after administration but diminishing during the studied time. Finally, lindane induced a decrease in [3 H]Mus binding, which became more evident over time. These modifications were observed both in the presence and in the absence of convulsions. However, an increase in [3 H]-Mus binding was detected shortly after lindane-induced convulsions. The observed decrease in [35 S]TBPS binding is in agreement with the postulated action of lindane at the picrotoxinin binding site of the GABAA receptor chloride channel. The effects observed on the binding of [3 H]Flu and [3 H]Mus may be secondary to the action of lindane as an allosteric antagonist of the GABAA receptor. 相似文献
6.
Kumlesh K. Dev Vibeke Petersen Tage Honoré Jeremy M. Henley 《Journal of neurochemistry》1996,67(6):2609-2612
Abstract: 6-Nitro-7-sulphamoylbenzo[ f ]quinoxaline-2,3-dione (NBQX) is a competitive antagonist selective for α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors. Here we report the pharmacological characteristics and anatomical distribution of [3 H]NBQX binding to rat brain. The association rate of [3 H]NBQX to rat cerebrocortical membranes was rapid, with peak binding occurring within 10 min at 0°C. The off-rate was also rapid, with near-complete dissociation of the radioligand within 5 min of addition of 1 m M unlabelled l -glutamate. [3 H]NBQX bound to a single class of sites with K D and B max values of 47 n M and 2.6 pmol mg−1 of protein, respectively. The rank order of inhibition of [3 H]NBQX binding by AMPA receptor ligands was NBQX ≫ 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) ≥ ( S )-5-fluorowillardiine ≥ AMPA ≫ l -glutamate. The chaotrope KSCN had no effect on the IC50 value of unlabelled NBQX displacement of [3 H]NBQX binding. The kainate receptor-selective ligands NS102 and kainate were only very weak displacers. It is interesting that NBQX and CNQX displaced significantly more [3 H]NBQX than any of the agonists tested. Autoradiographic analysis of the binding of [3 H]NBQX to coronal sections showed a distribution compatible with that of [3 H]AMPA binding. These data indicate that [3 H]NBQX provides a useful novel tool to characterise the antagonist binding properties of AMPA receptors. 相似文献
7.
G. de Montis K. Beaumont F. Javoy-Agid Y. Agid J. Constandinidis A. Lowenthal K. G. Lloyd 《Journal of neurochemistry》1982,38(3):718-724
Abstract: Specific [3 H]strychnine binding was used to identify the glycine receptor macromolecular complex in human spinal cord, substantia nigra, inferior olivary nucleus, and cerebral cortex. In material from control patients a high-affinity K d (3–8 n m ) was observed in the spinal cord and the substantia nigra, both the pars compacta and the pars reticulata. This is very similar to the values observed in the rat and bovine spinal cord (8 and 3 n m , respectively) and rat substantia nigra (12 n m ). In the human brain the distribution of [3 H]strychnine binding (at 10 n m ) was: spinal cord – substantia nigra, pars compacta > substantia nigra, pars reticulata = inferior olivary nucleus > cerebral cortex. The binding capacity ( B max ) of the rat brain (substantia nigra or spinal cord) was approximately 10-fold that of the human brain. [ 3 H]Strychnine binding was significantly decreased in the substantia nigra from Parkinson's disease patients, both in the pars compacta (67% of control) and the pars reticulata (50% of control), but not in the inferior olivary nucleus. The results were reproduced in a preliminary experiment in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. In the substantia nigra from patients who died with Huntington's disease, [3 H]strychnine binding tended to be high (150% of control, NS) in both the pars compacta and the reticulata. [3 H]Strychnine binding was unaltered in the substantia nigra of patients with senile dementia. Together with previous neurophysiological and neuropharmacological findings, those results support the hypothesis of glycine receptors occurring on dopamine cell bodies and/or dendrites in the substantia nigra. 相似文献
8.
Abstract: The kinetics and pharmacology of N G -nitro- l -[2,3,4,5-3 H]arginine ( l -[3 H]NOARG) binding to rat cerebellum were investigated using in vitro radioligand binding. Specific l -[3 H]NOARG binding in cerebellum was of nanomolar affinity, reversible, saturable, and best fit to a single-site model. Specific binding was Ca2+ dependent and sensitive to pH (with an optimum of 5.5–7.0). Added calmodulin (1.5–40 µg/ml) had no influence on specific l -[3 H]NOARG binding. However, the calmodulin antagonists W-5, W-13, and calmidazolium inhibited l -[3 H]NOARG binding with IC50 values in the micromolar range, and calmodulin (10 µg/ml) competitively reversed this inhibition. Nitric oxide synthase (NOS) inhibitors ( N G -nitro- l -arginine methyl ester and N G -monomethyl- l -arginine acetate) and l -arginine displaced l -[3 H]NOARG binding with IC50 values in the nanomolar range, whereas d -arginine and basic amino acids ( l -lysine and l -histidine) displaced l -[3 H]NOARG binding with IC50 values in the millimolar range. A comparison of the NOS functional assay with l -[3 H]NOARG binding in rat cerebellum showed similar profiles of Ca2+ dependency and inhibitory kinetics. Quantitative autoradiographic distribution of l -[3 H]NOARG binding sites was significantly higher in the molecular layer than in the granular layer of cerebellum. These studies confirm the potential use of l -[3 H]NOARG binding to study the regional distribution and functional properties of NOS. 相似文献
9.
Abstract: [3 H]Diazepam and [3 H]flunitrazepam ([3 H]FNP) binding to washed and frozen synaptosomal membranes from rat cerebral cortex were compared. In Tris-citrate buffer, γ -aminobutyric acid (GABA) and NaCl both increased [3 H]diazepam binding more than [3 H]FNP binding. GABA and pentobarbital both enhanced this effect of NaCl. Because of the extremely rapid dissociation of [3 H]diazepam in the absence of NaCl and GABA, the Bmax (maximal binding capacity) was smaller by the filtration assay than by the centrifugation assay. [3 H]FNP, which dissociates more slowly, had the same Bmax in both assays. [3 H]Diazepam association had two components, and was faster than [3 H]FNP association. [3 H]Diazepam dissociation, which also had two components, was faster than that of [3 H]FNP, and also had a greater fraction of rapidly dissociating species. [3 H]FNP dissociation was similar when initiated by diazepam, flunitrazepam, clonazepam, or Ro15-1788, which is a benzodiazepine antagonist. [3 H]Diazepam dissociation with Ro15-1788, flunitrazepam, or clonazepam was slower than with diazepam. GABA and NaCl, but not pentobarbital, increased the percentage of slowly dissociating species. This effect of NaCl was potentiated by GABA and pentobarbital. The results support the cyclic model of benzodiazepine receptors existing in two interconvertible conformations, and suggest that, distinct from their binding affinity, some ligands (like flunitrazepam) are better than others (like diazepam) in inducing the conversion of the receptor to the higher-affinity state. 相似文献
10.
Gino Giannaccini Claudia Martini Antonio Lucacchini Enrica Strettoi Marco Piccolino† 《Journal of neurochemistry》1993,61(4):1263-1269
Abstract: The binding of [3 H]flunitrazepam, [3 H]RO 5-4864, and [3 H]PK 11195 to membrane preparations of the retina was studied in the turtle and rabbit. Only a single population of [3 H]flunitrazepam binding sites was detected in the turtle, whereas two populations appeared to be present in the rabbit. No specific binding for [3 H]RO 5-4864 and [3 H]PK 11195 could be detected in the turtle. In rabbit, both ligands bound with high affinity, revealing a significant population of binding sites (KD values of 24 ± 2.3 and 2.2 ± 0.8 nM, and Bmax values of 440 ± 35 and 1,482 ± 110 fmol/mg of protein, respectively). The binding was temperature - and protein-dependent. Displacement studies showed a similar rank order of potency of various unlabeled ligands against both [3 H]RO 5-4864 and [3 H]PK 11195 (PK 11195 > Ro 5-4864 > flunitrazepam > flumazenil). These results suggest that peripheral-type benzodiazepine receptors are present in the retina of the rabbit, but not of the turtle. 相似文献
11.
Abstract: The nature of [3 H]imipramine binding to human platelets was investigated. Desipramine and 5-hydroxytryptamine (5-HT) displaced the same amount of binding and the binding was sensitive to protease treatment. The nature of pharmacological inhibition of [3 H]imipramine binding was investigated in saturation experiments. Increases in K d without changes in B max were noted with the addition of 5-HT, desipramine, norzimeldine, or 5-methoxytryptoline. Reductions in B max without alterations in K D were obtained when citalopram or clomipramine was added. It is concluded that the [3 H]imipramine binding site in human platelets is of protein nature and that this binding site contains the substrate recognition site for 5-HT uptake. In addition, [3 H]imipramine and other 5-HT uptake inhibitors have bonds to other parts of the 5-HT uptake carrier or to the surrounding lipid membrane. This additional binding outside the substrate recognition site is not one single site but most likely represents sites that are specific for the chemical structure of each uptake inhibitor, respectively. 相似文献
12.
Paulo F. Santos Maria S. Santos Arsélio P. Carvalho Carlos B. Duarte 《Journal of neurochemistry》1998,71(3):1086-1094
Abstract: We have investigated the effect of endogenous adenosine on the release of [3 H]acetylcholine ([3 H]ACh) in cultured chick amacrine-like neurons. The release of [3 H]ACh evoked by 50 m M KCl was mostly Ca2+ dependent, and it was increased in the presence of adenosine deaminase and in the presence of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), an adenosine A1 receptor antagonist. The effect of adenosine on [3 H]ACh release was sensitive to pertussis toxin (PTX) and was due to a selective inhibition of N-type Ca2+ channels. Ligand binding studies using [3 H]DPCPX confirmed the presence of adenosine A1 receptors in the preparation. Using specific inhibitors of the plasma membrane adenosine carriers and of the ectonucleotidases, we found that the extracellular accumulation of adenosine in response to KCl depolarization was due to the release of endogenous adenosine per se and to the extracellular conversion of released nucleotides into adenosine. Activation of adenosine A1 receptors was without effect on the intracellular levels of cyclic AMP under depolarizing conditions, but it inhibited the accumulation of inositol phosphates. Our results indicate that in cultured amacrine-like neurons, the Ca2+ -dependent release of [3 H]ACh evoked by KCl is under tonic inhibition by adenosine, which activates A1 receptors. The effect of adenosine on the [3 H]ACh release may be due to a direct inhibition of N-type Ca2+ channels and/or secondary to the inhibition of phospholipase C and involves the activation of PTX-sensitive G proteins. 相似文献
13.
Hoau-Yan Wang †Tian-Li Yue †‡Giora Feuerstein ‡ Eitan Friedman 《Journal of neurochemistry》1994,63(5):1720-1725
Abstract: The effect of platelet-activating factor (PAF) on neurotransmitter release from rat brain slices prelabeled with [3 H]acetylcholine ([3 H]ACh), [3 H]norepinephrine ([3 H]NE), or [3 H]serotonin ([3 H]5-HT) was studied. PAF inhibited K+ depolarization-induced [3 H]ACh release in slices of brain cortex and hippocampus by up to 59% at 10 n M but did not inhibit [3 H]ACh release in striatal slices. PAF did not affect 5-HT or NE release from cortical brain slices. The inhibition of K+ -evoked [3 H]ACh release induced by PAF was prevented by pretreating tissues with several structurally different PAF receptor antagonists. The effect of PAF was reversible and was not affected by pretreating brain slices with tetrodotoxin. PAF-induced inhibition of [3 H]ACh release was blocked 90 ± 3 and 86 ± 2% by pertussis toxin and by anti-Gαi1/2 antiserum incorporated into cortical synaptosomes, respectively. The results suggest that PAF inhibits depolarization-induced ACh release in brain slices via a Gαi1/2 protein-mediated action and that PAF may serve as a neuromodulator of brain cholinergic system. 相似文献
14.
Taurine Interactions with Chick Retinal Membranes 总被引:4,自引:4,他引:0
Abstract: Binding of [3 H]taurine to whole retinal membranes and to membranes obtained from retinal subcellular fractions was studied. [3 H]Taurine bound to chick retinal membranes with high affinity and specificity. Two types of [3 H]taurine binding associated to retinal membranes were observed, one with a KD = 0.68 μM and the other one with a KD ,= 9.32 μM. Both types of binding were highly Na− -dependent. The Na+ -dependent taurine binding was antagonized by strychnine. Bound [3 H]taurine was effectively displaced by β-alanine but not by GABA or glycine. Taurine binding was preferentially localized in membranes obtained from the crude synaptosomal fraction, although it is also present in substantial amounts in all retinal membranes. A Na+ -independent [3 H]taurine binding exhibiting properties which might represent interaction with postsynaptic receptor sites could not be demonstrated in the chick retina. 相似文献
15.
Abstract: In contrast to striatal membranes of adult rats, where high- ( K D1 = 34 n M ) and low- ( K D2 = 48,400 n M ) affinity binding sites for [3 H]WIN 35,428 are present, in primary cultures of ventral mesencephalon neurons (CVMNs) only low-affinity binding sites were found ( K D = 336,000 n M ). The binding of [3 H]WIN 35,428 in CVMNs prepared from rat embryos was reversible, saturable, and located in cytosol. Although dopamine (DA) uptake blockers inhibited [3 H]DA uptake at nanomolar concentrations in CVMNs, the displacement of [3 H]WIN 35,428 binding in CVMNs by DA uptake inhibitors required 100-8,000 times higher concentrations than were needed to displace [3 H]WIN 35,428 binding in striatal membranes. Piperazine derivatives, e.g., GBR-12909, GBR-12935, and rimcazole, inhibited [3 H]WIN 35,428 binding in CVMNs more effectively than did cocaine, WIN 35,428, mazindol, nomifensine, or benztropin. A positive correlation ( r = 0.779; p < 0.001) was found between drug affinities for the striatal membrane sites labeled by [3 H]WIN 35,428 and their abilities to inhibit DA uptake in CVMNs, whereas no correlation existed between the IC50 values of drugs that inhibited [3 H]WIN 35,428 binding and [3 H]DA uptake in CVMNs. The cytosolic [3 H]WIN 35,428 binding sites may be a piperazine acceptor and may not be involved in the regulation of the DA transporter. 相似文献
16.
Anissa Abi-Dargham Marc Laruelle David T. Wong David W. Robertson† Daniel R. Weinberger Joel E. Kleinman 《Journal of neurochemistry》1993,60(2):730-737
Abstract: Binding of [3 H]LY278584, which has been previously shown to label 5-hydroxytryptamine3 (5-HT3 ) receptors in rat cortex, was studied in human brain. Saturation experiments revealed a homogeneous population of saturable binding sites in amygdala ( K D = 3.08 ± 0.67 n M, B max = 11.86 ± 1.87 fmol/mg of protein) as well as in hippocampus, caudate, and putamen. Specific binding was also high in nucleus accumbens and entorhinal cortex. Specific binding was negligible in neocortical areas. Kinetic studies conducted in human hippocampus revealed a K on of 0.025 ± 0.009 n M −1 min−1 and a K off of 0.010 ± 0.002 min−1 . The kinetics of [3 H]LY278584 binding were similar in the caudate. Pharmacological characterization of [3 H]LY278584 specific binding in caudate and amygdala indicated the compound was binding to 5-HT3 receptors. We conclude that 5-HT3 receptors labeled by [3 H]LY278584 are present in both limbic and striatal areas in human brain, suggesting that 5-HT3 receptor antagonists may be able to influence the dopamine system in humans, similarly to their effects in rodent studies. 相似文献
17.
Abstract: The effect of Zn2+ on t -[3 H]butylbicycloorthobenzoate ([3 H]TBOB) binding to the GABAA receptor complex was studied autoradiographically in rat brain. Zn2+ inhibited [3 H]TBOB binding in a dose-dependent manner at physiological concentrations. Saturation analysis revealed noncompetitive inhibition in various brain regions. The inhibitory effect of Zn2+ had regional heterogeneity; regions showing the greatest inhibition of [3 H]TBOB binding were cortical laminae I–III, most areas of hippocampus, striatum, septum, and cerebellar cortex. Regions with relatively less inhibition of [3 H]TBOB binding included cortical laminae V–VI, thalamus, superior colliculus, inferior colliculus, and central gray matter. The effect of Zn2+ and those of other GABAA ligands, such as benzodiazepines, bicuculline, isoguvacine, and picrotoxin, on [3 H]TBOB binding seemed to be additive. Ni2+ , Cd2+ , and Cu2+ also inhibited [3 H]TBOB binding with a regional heterogeneity similar to that produced by Zn2+ . These results are consistent with Zn2+ acting at the previously detected recognition site on the GABAA receptor complex, distinct from the picrotoxin, GABA, and benzodiazepine sites. The regional heterogeneity of the Zn2+ effect may reflect differential regional distribution of GABAA receptor subtypes among brain regions. Other divalent cations probably act at the Zn2+ binding site. 相似文献
18.
Abstract— [125 I]Diiodo α-bungarotoxin ([125 I]2 BuTx) and [3 H]quinuclidinylbenzilate ([3 H]QNB) binding sites were measured in post-nuclear membrane fractions prepared from whole brains or brain regions of several species. Species studied included Drosophila melanogaster (fruit fly), Torpedo californiea (electric ray), Carassius auratus (goldfish), Ram pipiens (grass frog), Kana cutesheiana (bullfrog), Rattus norvegicus (rat, Sprague-Dawley), Mus muscalus (mouse, Swiss random, C58/J, LG/J), Oryctolagus cuniculus (rabbit, New Zealand Whitc), and Bos (cow). Acetyl-CoA: choline O -acetyltransferase (EC 2.3.1.6) levels were also determined in the post nuclear supernatants and correlated with the number of binding sites.
All species and regions except Drosophila had 16–150 fold more [3 H]QNB binding sites than [125 I]2 BuTx binding sites. Brain regions with the highest levels of [125 I]2 BuTx binding were Drosophila heads (300 fmol/mg), goldfish optic tectum (80fmol/mg), and rat and mouse hippocampus (3040 fmol/mg). The highest levels of [3 H]QNB binding were seen in rat and mouse caudate (1.3–1.6 pmol/mg). Lowest levels of [3 H]QNB and [125 I]2 BuTx binding were seen in cerebellum. The utility of [125 I]2 BuTx and [3 H]QNB binding as quantitative measures of nicotinic and muscarinic acetylcholine receptors in CNS is discussed. 相似文献
All species and regions except Drosophila had 16–150 fold more [
19.
F. Nicoletti M. L. Barbaccia M. J. Iadarola O. Pozzi H. E. Laird II 《Journal of neurochemistry》1986,46(1):270-273
Abstract: We found that the binding of [3 H]prazosin, a selective ligand for α1 -adrenergic recognition sites, is significantly lower in the frontal cortex of the genetically epilepsy-prone rats (GEPRs), as compared with normal Sprague-Dawley rats. Scatchard analysis reveals a decrease in the B max of [3 H]prazosin binding with no change in the apparent K D , suggesting that there are fewer α1 -adrenergic recognition sites in the frontal cortex of the GEPR. This abnormality is associated with a reduced capacity of norepinephrine (NE) to stimulate [3 H]inositol monophosphate ([3 H]IP1 ) formation in frontal cortex slices prelabeled with [3 H]inositol. No significant differences in [3 H]prazosin binding as well as NE-stimulated [3 H]IP1 formation have been observed in other brain regions including hippocampus, corpus striatum, and inferior colliculus. These results indicate that a deficit in the α1 -adrenergic receptor system in the frontal cortex may play a role in the seizure process in the GEPR. 相似文献
20.
Abstract: The ability of adenosine agonists to modulate K+ -evoked 4D†-[3 H]aminobutyric acid ([3 H]GABA) and acetylcholine (ACh) release from rat striatal synaptosomes was investigated. The A2a receptor-selective agonist CGS 21680 inhibited Ca2+ -dependent [3 H]GABA release evoked by 15 m M KCI with a maximal inhibition of 29 ± 4% (IC50 of ∼4 ± 10 −12 M ). The relative order of potency of three agonists was CGS 21680 ± 5'- N -ethylcarboxamidoadenosine > R-phenylisopropyladenosine (R-PIA), with the inhibition being blocked by A2a receptor-selective antagonists (CP 66,713 and CGS 15943A) but not by the A1 -selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). When release of [3 H]GABA was evoked by 30 mM KCI, no significant inhibition was observed. In contrast, CGS 21680 stimulated the release of [3 H]ACh evoked by 30 m M KCI, with a maximal stimulation of 26 ± 5% (IC50 of ∼10−11 M ). This effect was blocked by CP 66,713 but not by DPCPX. The A1 agonist R -PIA inhibited [3 H]ACh release, an effect blocked by DPCPX. It is concluded that adenosine A2a receptors are present on both GABAergic and cholinergic striatal nerve terminals where they inhibit and stimulate transmitter release, respectively. Key Words : GABA—Acetylcholine—Adenosine receptors—Striatum. 相似文献