Characterization of the binding of [3H](+)-pentazocine to σ recognition sites in guinea pig brain

DeHaven‐Hudkins, Diane L.; Fleissner, Lorraine C.; Ford-Rice, Felicia Y.

doi:10.1016/0922-4106(92)90153-m

Cited by 178 publications

(124 citation statements)

References 21 publications

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“…Early reports on association of G proteins with receptors were conflicting, with some investigators showing an association (Itzhak, 1989;Tokuyama et al, 1999;Hayashi et al, 2000;Meyer et al, 2002) and others refuting those assertions (DeHaven-Hudkins et al, 1992). The cloned receptor protein is too small to be a classic G protein-coupled receptor, and no recognition site is apparent from sequence analysis for the direct interaction of the 1 receptor with G proteins.…”

Section: Discussionmentioning

confidence: 99%

ς₁Receptor Agonist-Mediated Regulation ofN-Methyl-d-aspartate-Stimulated [³H]Dopamine Release Is Dependent upon Protein Kinase C

Nuwayhid

Werling²

2003

J Pharmacol Exp Ther

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We have previously shown that 1 receptor agonists inhibit N-methyl-D-aspartate (NMDA)-stimulated [ 3 H]dopamine from slices of rat striatum in a concentration-related manner and that the inhibition is reversed by 1 receptor-selective and nonsubtype-selective receptor antagonists. Based on previous evidence from our laboratory as well as other laboratories, we hypothesized that 1 receptors might use a protein kinase C (PKC) signaling pathway to modulate stimulated dopamine release. We tested several inhibitors of PKC isozymes, as well as a phospholipase C inhibitor for their effects on 1 receptor agonist-mediated regulation of [ 3 H]dopamine release. Although none of the inhibitors tested affected the ability of NMDA to stimulate [ 3 H]dopamine release, they all abolished regulation by the 1 receptor agonist (ϩ)-pentazocine in a concentrationrelated manner. We also found that prior exposure to 1 M phorbol 2-myristate 13-acetate for 30 min abolished regulation by (ϩ)-pentazocine. We concluded that an intact PKC system was required for 1 agonist-mediated regulation of NMDAstimulated [3 H]dopamine release from rat striatal slices. Based on the pharmacological profile of the PKC inhibitors tested, as well as reports in the literature on PKC involvement in neurotransmitter release and receptor action, PKC␤ seems most likely to be responsible, at least in part, for the effects of (ϩ)-pentazocine on dopamine release.

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Section: Discussionmentioning

confidence: 99%

ς₁Receptor Agonist-Mediated Regulation ofN-Methyl-d-aspartate-Stimulated [³H]Dopamine Release Is Dependent upon Protein Kinase C

Nuwayhid

Werling²

2003

J Pharmacol Exp Ther

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“…Assays of Akunne et al (1997) were performed at pH 8.0 and 25°C, where the K d of [ 3 H](1)-pentazocine was reported as 4.7 nM. Under the latter conditions, steady state was likely not attained (DeHaven-Hudkins et al, 1992). As reviewed by Hulme and Trevethick (2010), use of the Cheng-Prusoff (Cheng and Prusoff, 1973) (Lever et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…The in vitro s 1 receptor assays were performed at pH 7.4 and 37°C in guinea pig brain membranes, where the K d of [ 3 H](1)-pentazocine is 2.3-2.9 nM (DeHaven-Hudkins et al, 1992;Cobos et al, 2005;Lever et al, 2006). Assays of Akunne et al (1997) were performed at pH 8.0 and 25°C, where the K d of [ 3 H](1)-pentazocine was reported as 4.7 nM.…”

Section: Discussionmentioning

confidence: 99%

Relationship between Cerebral Sigma-1 Receptor Occupancy and Attenuation of Cocaine’s Motor Stimulatory Effects in Mice by PD144418

Lever

Miller

Fergason-Cantrell

et al. 2014

J Pharmacol Exp Ther

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Psychostimulant effects of cocaine are mediated partly by agonist actions at sigma-1 (s 1 ) receptors. Selective s 1 receptor antagonists attenuate these effects and provide a potential avenue for pharmacotherapy. However, the selective and high affinity s 1 antagonist PD144418 (1,2,3,6-tetrahydro-5-[3-(4-methylphenyl)-5-isoxazolyl]-1-propylpyridine) has been reported not to inhibit cocaine-induced hyperactivity. To address this apparent paradox, we evaluated aspects of PD144418 binding in vitro, investigated s 1 receptor and dopamine transporter (DAT) occupancy in vivo, and re-examined effects on locomotor activity. PD144418 displayed high affinity for s 1 sites (K i 0.46 nM) and 3596-fold selectivity over s 2 sites (K i 1654 nM) in guinea pig brain membranes. No appreciable affinity was noted for serotonin and norepinephrine transporters (K i .100 mM), and the DAT interaction was weak (K i 9.0 mM). In vivo, PD144418 bound to central and peripheral s 1 sites in mouse, with an ED 50 of 0.22 mmol/kg in whole brain. No DAT occupancy by PD144418 (10.0 mmol/kg) or possible metabolites were observed. At doses that did not affect basal locomotor activity, PD144418 (1, 3.16, and 10 mmol/kg) attenuated cocaine-induced hyperactivity in a dosedependent manner in mice. There was good correlation (r 2 5 0.88) of hyperactivity reduction with increasing cerebral s 1 receptor occupancy. The behavioral ED 50 of 0.79 mmol/kg corresponded to 80% occupancy. Significant s 1 receptor occupancy and the ability to mitigate cocaine's motor stimulatory effects were observed for 16 hours after a single 10.0 mmol/kg dose of PD144418.

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“…Investigation of the σ 1 -receptor affinity [16,17] [ 3 H]-(+)-Pentazocine binding to guinea pig brain membrane preparations was performed according to standard radioligand binding assays [17], which were slightly modified as described below.…”

Section: Performance Of the Assaymentioning

confidence: 99%

“…Therefore, the tertiary amines 2 d, e and 3 d, e were investigated for their σ 1 -receptor affinity. In the assay guinea pig brain homogenates were used as receptor source and the 1-selective ligand [ 3 H]-(+)-pentazocine was employed as radioligand [16,17]. In the initial screening 1 µM solutions of the test compounds were incubated with the receptor preparation and the radioligand and the radioactivity trapped on the filters was determined.…”

mentioning

confidence: 99%

Synthesis and NMDA‐Receptor Affinity of Ring and Side Chain Homologous Dexoxadrol Derivatives

Aepkers¹,

Wünsch²

2004

Archiv der Pharmazie

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The regioselectivity during transacetalization of benzophenone dimethyl acetal (4) with butane-1, 2, 4-triol (5) is controlled by the reaction conditions. Thermo-dynamic control leads predominantly to the 1, 3-dioxolane 6 whereas kinetic control favors the six-membered acetal 7. The amines 2a-e and 3a-e are synthesized from the alcohols 6 and 7 and are investigated in receptor binding studies with radioligands for their affinity to the phencyclidine binding site of the NMDA-receptor. In both series the primary amines 2a and 3a show the highest NMDA-receptor affinity (2a: Ki=3.38 microM; 3a: Ki=1.45 microM). The NMDA receptor slightly prefers the 1, 3-dioxane derivatives 3a and 3b compared to 2a and 2b (factor 2-3). Low interactions of the amines 3a and 3b with various receptor and reuptake systems indicate selectivity for the NMDA receptor. Surprisingly, the piperidine derivative 2e binds with high affinity at sigma1-receptors and, therefore, represents a novel lead compound for high affinity sigma1-receptor ligands.

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Characterization of the binding of [3H](+)-pentazocine to σ recognition sites in guinea pig brain

Cited by 178 publications

References 21 publications

ς₁Receptor Agonist-Mediated Regulation ofN-Methyl-d-aspartate-Stimulated [³H]Dopamine Release Is Dependent upon Protein Kinase C

ς₁Receptor Agonist-Mediated Regulation ofN-Methyl-d-aspartate-Stimulated [³H]Dopamine Release Is Dependent upon Protein Kinase C

Relationship between Cerebral Sigma-1 Receptor Occupancy and Attenuation of Cocaine’s Motor Stimulatory Effects in Mice by PD144418

Synthesis and NMDA‐Receptor Affinity of Ring and Side Chain Homologous Dexoxadrol Derivatives

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Characterization of the binding of [3H](+)-pentazocine to σ recognition sites in guinea pig brain

Cited by 178 publications

References 21 publications

ς1Receptor Agonist-Mediated Regulation ofN-Methyl-d-aspartate-Stimulated [3H]Dopamine Release Is Dependent upon Protein Kinase C

ς1Receptor Agonist-Mediated Regulation ofN-Methyl-d-aspartate-Stimulated [3H]Dopamine Release Is Dependent upon Protein Kinase C

Relationship between Cerebral Sigma-1 Receptor Occupancy and Attenuation of Cocaine’s Motor Stimulatory Effects in Mice by PD144418

Synthesis and NMDA‐Receptor Affinity of Ring and Side Chain Homologous Dexoxadrol Derivatives

Contact Info

Product

Resources

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ς₁Receptor Agonist-Mediated Regulation ofN-Methyl-d-aspartate-Stimulated [³H]Dopamine Release Is Dependent upon Protein Kinase C

ς₁Receptor Agonist-Mediated Regulation ofN-Methyl-d-aspartate-Stimulated [³H]Dopamine Release Is Dependent upon Protein Kinase C