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  • 1
    Electronic Resource
    Electronic Resource
    Dopamine receptor modulation by conformationally constrained analogs of Pro-Leu-Gly-NH2 (1988)
    s.l. : American Chemical Society
    Journal of medicinal chemistry 31 (1988), S. 1430-1436 
    Details
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/jm00402a031
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  • 2
    Electronic Resource
    Electronic Resource
    Interaction of l-Prolyl-l-Leucyl Glycinamide with Dopamine D2 Receptor: Evidence for Modulation of Agonist Affinity States in Bovine Striatal Membranes (1988)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 50 (1988), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The role of the hypothalamic tripeptide l-prolyl-l-leucyl-glycinamide (PLG) in modulating the agonist binding to bovine striatal dopamine D2 receptor was investigated using a selective high-affinity agonist, n-propylnor-apomorphine (NPA). PLG caused an enhancement in [3H]NPA binding in striatal membranes in a dose-dependent manner, the maximum effect being observed at 10--7--10--6M concentration of the tripeptide. The Scat-chard analysis of [3H]NPA binding to membranes preincu-bated with 10--6M PLG revealed a significant increase in the affinity of the agonist binding sites. In contrast, there was no effect of PLG on the binding pattern of the antagonist [3H]spiroperidol. The antagonist versus agonist competition curves analyzed for agonist high- and low-affinity states of the receptor displayed an increase in the population and affinity of the high-affinity form of the receptor with PLG treatment. The low-affinity sites concomitantly decreased with relatively small change in the affinity for the agonists. Almost similar results were obtained when either NPA or apomorphine was used in the competition experiments. A partial antagonistic effect of PLG on 5′-guanylyl-imidodiphosphate [Gpp(NH)p]-induced inhibition of high-affinity agonist binding was also observed, as the ratio of high- to low-affinity forms of the receptor was significantly higher in the PLG-treated membranes compared to the controls. Direct [3H]NPA binding experiments demonstrated that PLG attenuated the Gpp(NH)p-induced inhibition of agonist binding by increasing the EC50 of the nu-cleotide (concentration that inhibits 50% of the specific binding). No effect of PLG on high-affinity [3H]NPA binding, however, could be observed when the striatal membranes were preincubated with Gpp(NH)p. The binding of antagonists and agonists to α2 adrenergic receptors, negatively coupled to adenylate cyclase in the striatum. was not affected by PLG. The results suggest that PLG modulates the affinity states of the dopamine D2 receptor, possibly by enhancing its interaction with the guanine nucleotide regulatory protein.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1988.tb03005.x
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  • 3
    Electronic Resource
    Electronic Resource
    Characterization of High-Affinity Dopamine D2 Receptors and Modulation of Affinity States by Guanine Nucleotides in Cholate-Solubilized Bovine Striatal Preparations (1986)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 47 (1986), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract 3,4-Dihydroxyphenylethylamine (dopamine) D2 receptors, solubilized from bovine striatal membranes using a cholic acid-NaCl combination, exhibited the typical pharmacological characteristics of both agonist and antagonist binding. The rank order potency of the agonists and antagonists to displace [3H]spiroperidol binding was the same as that observed with membrane-bound receptors. Computer-assisted analysis of the [3H]spiroperidol/agonist competition curves revealed the retention of high- and low-affinity states of the D2 receptor in the solubilized preparations and the proportions of receptor subpopulations in the two affinity states were similar to those reported in membrane. Guanine nucleotide almost completely converted the high-affinity sites to low-affinity sites for the agonists. The binding of the high-affinity agonist [3H]N-n-propylnor-apomorphine ([3H]NPA) was clearly demonstrated in the solubilized preparations for the first time. Addition of gua-nylyl-imidodiphosphate completely abolished the [3H]NPA binding. When the solubilized receptors were subjected to diethylaminoethyl-Sephacel chromatography, the dopaminergic binding sites eluted in two distinct peaks, showing six- to sevenfold purification of the receptors in the major peak. Binding studies performed on both peaks indicated that the receptor subpopulation present in the first peak may have a larger proportion of high-affinity binding sites than the second peak. The solubilized preparation also showed high-affinity binding of [35S]guanosine-5′-(γ-thio)triphos-phate, a result suggesting the presence of guanine nucleotide binding sites, which may interact with the solubilized D2 receptors. These data are consistent with the retention of the D2 receptor-guanine nucleotide regulatory protein complex in the solubilized preparations and should provide a suitable model system to study the receptor-effector interactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.1986.tb00784.x
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of neonatal ventral hippocampal lesion in rats on stress-induced acetylcholine release in the prefrontal cortex (2004)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 91 (2004), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Excitotoxic neonatal ventral hippocampus (NVH) lesions in rats result in characteristic post-pubertal hyper-responsiveness to stress and cognitive abnormalities analogous to those described in schizophrenia and suggestive of alterations in dopamine (DA) neurotransmission. Converging lines of evidence also point to dysfunctions in the cortical cholinergic system in neuropsychiatric disorders. In previous studies, we observed alterations in dopaminergic modulation of acetylcholine (Ach) release in the prefrontal cortex (PFC) in post-pubertal NVH-lesioned rats. These two neurotransmitter systems are involved in the stress response as PFC release of DA and Ach is enhanced in response to some stressful stimuli. As adult NVH-lesioned rats are behaviorally more reactive to stress, we investigated the effects of NVH lesions on tail-pinch stress-induced Ach and DA release in the PFC. Using in vivo microdialysis, we observed that tail-pinch stress resulted in significantly greater increases in prefrontal cortical Ach release in post-pubertal NVH-lesioned rats (220% baseline) compared with sham-operated controls (135% baseline). Systemic administration of the D1-like receptor antagonist SCH 23390 (0.5 mg/kg i.p.) or the D2-like receptor antagonist haloperidol (0.2 mg/kg i.p.), as well as intra-PFC administration of the D2-like antagonist sulpiride (100 µm), reduced stress-induced Ach release in PFC of adult NVH-lesioned rats. By contrast, intra-PFC administration of SCH 23390 (100 µm) failed to affect stress-induced Ach release in PFC of NVH-lesioned rats. Interestingly, using in vivo voltammetry, stress-induced stimulation of PFC DA release was found to be attenuated in adult NVH-lesioned rats. Taken together, these data suggest developmentally specific reorganization of prefrontal cortical cholinergic innervation notably regarding its regulation by DA neurotransmission.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.2004.02831.x
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  • 5
    Electronic Resource
    Electronic Resource
    Alterations in dopaminergic modulation of prefrontal cortical acetylcholine release in post-pubertal rats with neonatal ventral hippocampal lesions (2004)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 89 (2004), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Excitotoxic lesion of the ventral hippocampus in neonatal rats is a putative animal model of schizophrenia with characteristic developmental abnormalities in dopaminergic neurotransmission and prefrontal cortical functions. Converging evidence also points to the involvement of the central cholinergic system in neuropsychiatric disorders. These two neurotransmitter systems are interlinked in the prefrontal cortex (PFC) where dopamine stimulates acetylcholine (ACh) release. In the present study, we investigated the role of dopamine in the developmental regulation of prefrontal cortical ACh release and the expression of nicotinic and muscarinic receptors in pre- and post-pubertal rats with neonatal ibotenic acid-induced lesions of the ventral hippocampus (NVH). In vivo microdialysis in the PFC revealed that systemic injections of the D1-like receptor agonist (±)-6-chloro-7,8-dihydroxy-1-phenyl2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 81297) (2.5 and 5.0 mg/kg i.p.) caused significantly higher ACh release in post-pubertal NVH-lesioned animals (250 and 300% baseline for 2.5 and 5.0 mg/kg, respectively) compared with post-pubertal shams (150 and 220% baseline for 2.5 and 5.0 mg/kg, respectively). Most interestingly, while prefrontal cortical perfusion of SKF 81297 (100 and 250 µm) had no significant effect on ACh release in post-pubertal sham-operated animals, it significantly stimulated ACh release to approximately 250% baseline at both doses in post-pubertal NVH-lesioned animals. Receptor autoradiography demonstrated a significant and selective increase in M1-like receptor binding sites in the infralimbic area of the PFC in the post-pubertal NVH-lesioned animals. For all experiments, significant differences between sham and NVH-lesioned animals were observed only in post-pubertal rats. These results suggest a developmentally specific reorganization of the prefrontal cortical cholinergic system involving D1-like receptors in the NVH model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.2004.02351.x
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  • 6
    Electronic Resource
    Electronic Resource
    Strain differences in the behavioural outcome of neonatal ventral hippocampal lesions are determined by the postnatal environment and not genetic factors (2001)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 14 (2001), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It has been demonstrated that not only do rats neonatally lesioned in the ventral hippocampus (VH) develop behavioural hypersensitivity to amphetamine postpubertally, but also that the expression of the sensitivity is strain specific. For example, excitotoxic VH lesions at postnatal day (PD) 7 lead to significant increases in amphetamine-induced locomotion in postpubertal Fischer rats, but not in Lewis rats. However, as it is likely that the effect of strain differences are due to a combination of genetics and environment, we examined the contributions of the environment of the pups in determining the behavioural outcome following neonatal VH lesions. Fisher and Lewis rat pups were cross-fostered at birth, and then at PD7 lesioned bilaterally in the VH with ibotenic acid. anova analysis of postpubertal amphetamine-induced locomotor data revealed a significant effect of the strain of the dams raising the pups but no effect of the strain of the pup. In addition, a post hoc analysis revealed that lesioned Fisher or Lewis rats raised by Fisher, but not those raised by Lewis, dams demonstrated amphetamine-induced hyperlocomotion relative to nonlesioned controls. Observations of the maternal behaviour of Fischer and Lewis dams revealed significant differences in the frequency of arched-back nursing between the two strains. Interestingly, a correlation of the frequency of arched back nursing vs novelty- or amphetamine-induced locomotion revealed that the lesioned rats were significantly more affected by increases in arched-back nursing compared to the controls. The results suggest that the genetic background of the pups does not significantly affect the behavioural outcome following neonatal VH lesions; however, the results do suggest an important role of early environmental variables on the behavioural outcome of neonatal VH lesions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.0953-816x.2001.01716.x
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  • 7
    Electronic Resource
    Electronic Resource
    Solubilization and reconstitution of dopamine D1 receptor from bovine striatal membranes: Effects of agonist and antagonist pretreatment (1990)
    Springer
    Neurochemical research 15 (1990), S. 647-657 
    Details
    ISSN: 1573-6903
    Keywords: [3H]SCH-23390 ; dopamine D1 receptor ; bovine striatum ; solubilization ; guanine nucleotides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The bovine striatal dopamine D1 receptor was solubilized with a combination of sodium cholate and NaCl in the presence of phospholipids, following treatment of membranes with a dopaminergic agonist (SKF-82526-J) or antagonist (SCH-23390). The solubilized receptors were subsequently reconstituted into lipid vesicles by gel-filtration. A comparison of ligand-binding properties shows that the solubilized and reconstituted receptors bound [3H]SCH-23390 to a homogeneous site in a saturable, stereospecific and reversible manner with a Kd of 0.95 and 1.1 nM and a Bmax of 918 and 885 fmol/mg protein respectively for agonist- and antagonist-pretreated preparations. These values are very similar to those obtained for membrane-bound receptors. The competition of antagonists for [3H]SCH-23390 binding exhibited a clear D1 dopaminergic order in the reconstituted preparation obtained from either agonist or antagonist-pretreated membranes, except that (+)butaclamol was about four-fold more potent thancis-flupentixol in displacing [3H]SCH-23390 binding in preparation obtained from agonist-pretreated membranes compared to antagonist-pretreated membranes. The agonist/[3H]SCH-23390 competition studies revealed the presence of a highaffinity component of agonist binding in both the reconstituted receptor preparations. The number of high-affinity agonist binding sites, however, is 40–80% higher in reconstituted preparation obtained from antagonist-treated membrane compared to that obrained from the agonist-treated membrane. In both the preparations, 100 μM guanylylimidodiphosphate (Gpp(NH)p) completely abolished the high-affinity component of agonist binding compared to partial abolition in the native membranes, indicating a close association of a G-protein with the solubilized receptors. Whether the receptor was solubilized following agonist or antagonist preincubation of the membranes, the receptor-detergent complex eluted from a steric-exclusion HPLC column with an apparent molecular size of 360,000. Preincubation of the solubilized preparations with Gpp(NH)p had virtually no effect on the elution profile suggesting a lack of guanine nucleotide-dependent dissociation of G-protein receptor complex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00973757
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