European Journal of Pharmacology: Molecular Pharmacology最新文献

{"title":"Pharmacological study of dihydroetorphine in cloned μ-, δ- and κ-opioid receptors","authors":"Seishi Katsumata ,&nbsp;Masabumi Minami ,&nbsp;Takayuki Nakagawa ,&nbsp;Tatsunori Iwamura ,&nbsp;Masamichi Satoh","doi":"10.1016/0922-4106(95)90078-0","DOIUrl":"https://doi.org/10.1016/0922-4106(95)90078-0","url":null,"abstract":"<div><p>We investigated the binding characteristics of dihydroetorphine, 7,8-dihydro-7α-[1-(R)-hydroxyl-1-methylbutyl]-6,14-endoethano-tetrahydro-oripavine, and its effect on the inhibitory system of cyclic AMP production using cloned μ-, δ- and κ-opioid receptors expressed on Chinese hamster ovary cells. The <em>K</em>_i values of dihydroetrophine for the μ-, δ- and κ-opioid receptor were 4.5 × 10⁻¹⁰, 1.8 × 10⁻⁹ and 5.7 × 10⁻¹⁰ M, respectively. On the hand, those of morphine were 1.9 × 10⁻⁹, 1.4 × 10⁻⁶ and 1.3 × 10⁻⁷ M, respectively. Through all of these three types of opioid receptors, dihydroetorphine inhibited forskolin (10 μM)-stimulated cyclic AMP production via pertussis toxin-sensitive G protein(s), and the inhibitory effects were antagonized by co-application with opioid receptor antagonists. The IC₅₀ values of dihydroetorphine for the inhibition of cyclic AMP production through the μ-, δ- and κ-opioid receptors were 4.2 × 10⁻¹¹, 8.6 × 10⁻¹⁰ and 4.3 × 10⁻⁹ M, respectively. On the other hand, those of morphine were 2.6 × 10⁻⁸, 2.6 × 10⁻⁶ and 1.9 × 10⁻⁶ M, respectively. These results indicate that dihydroetorphine, unlike morphine which preferentially binds the μ-opioid receptor, binds not only μ- but also δ- and κ-opioid receptors with high affinity and acts as a more potent agonist than morphine for all of the three types of receptors.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 367-373"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90078-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71828299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NS-49, a novel α1a-adrenoceptor-selective agonist characterization using recombinant human α1-adrenoceptors","authors":"Kenji Obika ,&nbsp;Katsushi Shibata ,&nbsp;Kuniko Horie ,&nbsp;Rudolf Foglar ,&nbsp;Kiyoshi Kimura ,&nbsp;Gozoh Tsujimoto","doi":"10.1016/0922-4106(95)90073-X","DOIUrl":"https://doi.org/10.1016/0922-4106(95)90073-X","url":null,"abstract":"<div><p><em>α</em>₁-Adrenoceptors comprise a heterogeneous family and subtype-selective ligands are valuable in studying the functional role of each receptor subtype. Using the Chinese hamster ovary (CHO) cells stably expressing the cloned human <em>α</em>₁-adrenoceptor subtypes (<em>α</em>_1a, <em>α</em>_1b, and <em>α</em>_1d)¹, we have compared a newly synthesized phenethylamine class agonist (R)-(−)-3′-(2-amino-1-hydroxythyl)-4′- fluoromethanesulfonanilide hydrochloride (NS-49) with imidazoline class agonist oxymetazoline in their binding affinities and intrinsic activities in causing transient increases of cytosolic Ca²⁺ concentrations ([Ca²⁺]₁ response). Radioligand binding sites with 2-[β-(4-hydroxy-3-[¹²⁵I]iodophenyl)ethylamino-methyl]tetralone ([¹²⁵I]HEAT) showed NS-49 and oxymetazoline had higher affinities at <em>α</em>_1a- than at <em>α</em>_1b- and <em>α</em>_1d-subtypes (−<em>log</em> <em>K</em>_i values at <em>α</em>_1a−, <em>α</em>_1b− and <em>α</em>_1d-subtype: 6.18, 5.13, and 5.38 for NS-49; 8.19, 6.50, and 6.44 for oxymetazoline, respectively). In functional studies, both oxymetazoline and NS-49 worked as a selective and partial agonist at <em>α</em>_1a-subtype; however, NS-49 is more efficacious than oxymetazoline. NS-49 is the phenethylamine class of <em>α</em>₁-adrenoceptor partial agonist relatively selective and efficacious for the human <em>α</em>_1a-adrenoceptor subtype. NS-49 would be potentially useful for studying the physiological role of <em>α</em>₁-adrenoceptor subtype.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 327-334"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90073-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71828777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Additivity and non-additivity between dopamine-, norepinephrine-, carbachol- and GABA-stimulated GTPase activity","authors":"Yuji Odagaki,&nbsp;Sarmila Dasgupta,&nbsp;Kjell Fuxe","doi":"10.1016/0922-4106(95)90064-0","DOIUrl":"10.1016/0922-4106(95)90064-0","url":null,"abstract":"<div><p>The mode of coupling between neurotransmitter receptors and G proteins was investigated by agonist-induced high-affinity GTPase activity in rat striatal membranes. There was simple additive relationship among dopamine-, carbachol-, and γ-aminobutyric acid (GABA)-sensitive high-affinity GTPase activity in any combination, indicating that the respective receptors stimulated by these agonists (i.e., dopamine D₂, pirenzepine-insensitive muscarinic, and GABA_B receptors) interact independently with distinct pools of G proteins. Unexpectedly non-additivity was observed between dopamine- and norepinephrine-stimulation. This lack of additivity was apparently due to stimulation of the same dopamine D₂ receptors by both dopamine and norepinephrine, since norepinephrine-stimulated high-affinity GTPase activity could be inhibited by dopaminergic but not adrenergic antagonists. The same non-additivity as seen in rat striatum was confirmed in the membranes prepared from cultured mouse fibroblast cells co-transfected with dopamine D₂ and adenosine A_2A receptors. The implication of the (non-)additivity between receptor-mediated high-affinity GTPase activity was discussed with a consideration of the possible underlying molecular mechanism.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 245-253"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90064-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19692841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of berbamine on cytosolic phospholipase A2 activation in rabbit platelets","authors":"Satoshi Akiba,&nbsp;Ryo Nagatomo,&nbsp;Tsuyoshi Ishimoto,&nbsp;Takashi Sato","doi":"10.1016/0922-4106(95)90075-6","DOIUrl":"10.1016/0922-4106(95)90075-6","url":null,"abstract":"<div><p>The effect of berbamine, a biscoclaurine alkaloid, on cytosolic phospholipase A₂ activation in rabbit platelets was investigated. Berbamine inhibited árachidonic acid liberation induced by thrombin but not that by ionomycin. The alkaloid did not affect thrombin-stimulated Ca²⁺ mobilization, Ca²⁺-dependent translocation of cytosolic phospholipase A₂ to membranes, or the activity of partially purified cytosolic phospholipase A₂. Furthermore, berbamine had no effect on the thrombin-elicited increase in cytosolic phospholipase A₂ activity. However, berbamine suppressed arachidonic acid liberation in platelets stimulated with GTP-binding protein activators. Although incubation of platelet membranes with a GTP analogue decreased the islet-activating protein-catalyzed ADP-ribosylation of an approximately 40 kDa protein in the membranes, pretreatment of the membranes with berbamine did not influence the decrease in ADP-ribosylation. These results suggest that berbamine may impair GTP-binding protein-mediated activation of cytosolic phospholipase A₂, probably without influencing the enzyme translocation to membranes or the increase in the enzyme activity, and thus may cause the suppression of thrombin-induced arachidonic acid liberation.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 343-350"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90075-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19693372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural dependence of the allosteric interaction of semi-rigid verapamil analogues with dihydropyridine-binding in kitten heart","authors":"Werner Voigt ,&nbsp;M. Novella Romanelli ,&nbsp;Horst Lemoine ,&nbsp;Raimund Mannhold ,&nbsp;Silvia Dei ,&nbsp;Elisabetta Teodori ,&nbsp;Fulvio Gualtieri","doi":"10.1016/0922-4106(95)90065-9","DOIUrl":"10.1016/0922-4106(95)90065-9","url":null,"abstract":"<div><p>Structural determinants of the allosteric interaction of semi-rigid verapamil analogues with dihydropyridine binding were investigated in kitten heart using [³H](+)-isradipine as radioligand. Chemical variations were performed in the alkyl chain of verapamil and include introduction of unsaturation (double or triple bonds) or the insertion of cyclohexyl moieties. Introduction of unsaturation generally reduces the allosteric interaction in the case of ‘double bond’ - and abolishes it in the case of ‘triple bond’ - derivatives. Also the introduction of cyclohexyl moieties diminishes the potency of allosteric interaction: derivatives with the phenylethylamino side chain in an equatorial position exhibit the allosteric interaction, while it is lacking in derivatives with the basic side chain in axial position. Thus, the reduced conformational flexibility of the new verapamil congeners reduces or abolishes their ability to allosterically interfere with dihydropyridine binding. A molecular interpretation was approached by molecular modelling studies. The strategy was to find low energy conformations common to the active congeners, but not shared by the inactive ones. Structural features discriminating allosterically active and inactive congeners comprise: 1) the position of the nitrogen, 2) the volume occupied by the N-methyl groups, 3) the direction of the N-H bond and 4) the position of the phenyl ring in the basic side chain.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 255-264"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90065-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19693422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of caffeine on Ca2+ fluxes and secretion in bovine chromaffin cells","authors":"Pei-Shan Liu ,&nbsp;Yi-Jen Lin ,&nbsp;Lung-Sen Kao","doi":"10.1016/0922-4106(95)90066-7","DOIUrl":"10.1016/0922-4106(95)90066-7","url":null,"abstract":"<div><p>The effects of caffeine on Ca²⁺ fluxes and catecholamine secretion in bovine adrenal chromaffin cells were examined. Caffeine inhibited secretion, ⁴⁵Ca²⁺ uptake and cytosolic Ca²⁺ concentration ([Ca²⁺]_i) rise induced by the nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) and the Na⁺ channel activator veratridine. The inhibitory effect of caffeine on high K⁺-induced secretion was smaller than that on DMPP- and veratridine-induced responses. Caffeine only slightly inhibited high K⁺-induced ⁴⁵Ca²⁺ uptake and did not affect [Ca²⁺]_i rise. Caffeine also inhibited muscarinic receptor-mediated inositol phosphate generation. Our results suggest that the inhibitory effects of caffeine on bovine chromaffin cells mainly occur at both muscarinic and nicotinic receptors as well as at the voltage-dependent Na⁺ channels and to a smaller extent at site(s) distal to Ca²⁺ entry. The effects of caffeine on nicotinic receptors but not on muscarinic receptors can be explained by its ability to raise intracellular cAMP.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 265-272"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90066-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19693423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modest reduction of benzodiazepine binding in rat brain in vivo induced by antisense oligonucleotide to GABAA receptor γ2 subunit subtype","authors":"Jesper Karle,&nbsp;Mogens Nielsen","doi":"10.1016/0922-4106(95)90088-8","DOIUrl":"https://doi.org/10.1016/0922-4106(95)90088-8","url":null,"abstract":"<div><p>The GABA_A (γ-aminobutyric acid-A) receptor <em>γ</em>₂ subunit subtype is functionally integral part of the benzodiazepine binding site of the GABA_A receptor complex, important for benzodiazepine pharmacology. We have evaluated the possibility of specifically reducing benzodiazepine receptor binding properties in vivo using phosphorothioate antisense oligodeoxynucleotides to inhibit the expression of GABA_A receptor <em>γ</em>₂ subinit subtype. Intracerebroventricular infusions of an antisense oligonucleotide reduced benzodiazepine receptor radioligand binding by 9–15% in specific rat brain regions.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 439-441"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90088-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71785492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of α-helicity, amphipathicity and D-amino acid incorporation on the peptide-induced mast cell activation","authors":"L.J.Mark Cross ,&nbsp;Madeleine Ennis ,&nbsp;Aberhard Krause ,&nbsp;Margitta Dathe ,&nbsp;Dorothea Lorenz ,&nbsp;Gerd Krause ,&nbsp;Michael Beyermann ,&nbsp;Michael Bienert","doi":"10.1016/0922-4106(95)90069-1","DOIUrl":"https://doi.org/10.1016/0922-4106(95)90069-1","url":null,"abstract":"<div><p>Mast cell activation by polycationic substances is believed to result from a direct activation of G protein α subunits and it was suggested that the adaption of amphipathic, α-helical conformations wouuld allow the peptide to reach the cytosolic compartment to interact with G proteins (Mousli et al., 1994, Immunopharmacology 27, 1, for review). We investigated the histamine-releasing activity of model peptides as well as analogues of magainin 2 amide and neuropeptide Y with different amphipathicities and α-helix content on rat peritoneal mast cells. Amphipathic helicity is not a prerequisite for mast cell activation. Moreover, non-helical magainin peptides with high histamine-releasing activity were less active in the liberation of carboxyfluorisceine from negatively charged liposomes, indicating that peptide-induced mast cell activation and peptide-induced membrane perturbation do not correlate. In contrast to the negligible influence of the secondary structure, amino acid configuration may exert a striking influence on peptide-induced mast cell activation. Thus histamine-release by substance P was markedly impaired when the L-amino acids in the positively charged N-terminal region were replaced by D-amino acids, with [D-Arg¹]substance P being the most inactive substance P diastereoisomer.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 291-300"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90069-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71828301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potentiation and inhibition of subtypes of neuronal nicotinic acetylcholine receptors by Pb2+","authors":"Ruud Zwart,&nbsp;Regina G.D.M. Van Kleef,&nbsp;Jacob M. Milikan,&nbsp;Marga Oortgiesen,&nbsp;Henk P.M. Vijverberg","doi":"10.1016/0922-4106(95)90082-9","DOIUrl":"10.1016/0922-4106(95)90082-9","url":null,"abstract":"<div><p>Effects of inorganic lead (Pb²⁺) on defined subtypes of neuronal nicotinic acetylcholine receptors have been investigated. Voltage clamp experiments have been performed on <em>Xenopus</em> oocytes expressing α3β2, α3β4 and α4β2 neuronal nicotinic acetylcholine receptor subunit combinations. In oocytes expressing the α3β2 subunit combination Pb²⁺ enhances the peak amplitude of nicotinic acetylcholine receptor-mediated inward currents evoked by superfusion with 100 μM acetylcholine. At concentrations of 1–250 μM, Pb²⁺ potentiates α3β2 receptor-mediated inward current concentration dependently by a factor of 1.1–11.0. Inward currents evoked by low (3 μM) and high (1 mM) concentrations of acetylcholine are potentiated to a similar extent. Conversely, in oocytes expressing the α3β4 subunit combination Pb²⁺ inhibits the nicotinic receptor-mediated inward currents evoked with μM acetylcholine. Inhibitory effects are observed in the concentration range of 1 nM–100 μM Pb²⁺, but the degree of inhibition varies between oocytes. A similar inhibition of the α4β2 nicotinic receptor-mediated inward current by Pb²⁺ indicates that α as well as β subunits are involved in the potentiating and inhibitory effects. Possible reasons for the variation in the inhibitory effects of Pb²⁺ on α3β4 and α4β4 nicotinic receptor-mediated inward currents have been investigated and are discussed. The divalent cations Ca²⁺ and Mg²⁺ potentiate both α3β2 and α3β4 nicotinic receptor-mediated inward currents. The distinct modulation of receptor function by Pb²⁺ and by Ca²⁺ and Mg²⁺ and the dependence of the modulatory effect of Pb²⁺ on subunit composition suggest that Pb²⁺ interacts with multiple sites on the α and β subunits of neuronal nicotinic acetylcholine receptors.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 399-406"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90082-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19692554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[3H]1-aminocyclopropanecarboxylic acid, a novel probe for strychnine-insensitive glycine receptors","authors":"Piotr Popik ,&nbsp;Anita Lewin ,&nbsp;Berthold Berrang ,&nbsp;Gabriel Nowak ,&nbsp;Richard Layer ,&nbsp;Phil Skolnick","doi":"10.1016/0922-4106(95)90061-6","DOIUrl":"10.1016/0922-4106(95)90061-6","url":null,"abstract":"<div><p>[³H]1-Aminocyclopropanecarboxylic acid (ACPC) exhibits high affinity, specific binding to strychnine-insensitive glycine receptors. In extensively washed rat forebrain membranes, the specific binding of [³H]ACPC was optimal at 25°C in the presence of 10 mM MgCl₂. Comparable levels of specific [³H]ACPC binding were obtained using centrifugation and filtration for separation of bound from free radioligand. [³H]ACPC labels two sites with <em>K</em>_d1 and <em>B</em>_max1 values of 129±34 nM and 2.30±0.37 pmol/mg protein and <em>K</em>_d2 and <em>B</em>_max2 values of 7.26±1.69 <em>μ</em>M and 20.6±2.2 pmol/mg protein for the high and low affinity sites, respectively. The <em>K</em>_d of [³H]ACPC (66 nM) estimated under non-equilibrium conditions (<em>k</em>_off=8.91±0.78×10⁻³ s⁻¹; <em>k</em>_on=1.35×10⁻⁴ nM⁻¹ s⁻¹) was similar to the value obtained for the high affinity site obtained by equilibrium binding. The <em>K</em>_d1 of [³H]ACPC is in good agreement with the previously reported <em>K</em>_i values of ACPC to inhibit the binding of other glycinergic ligands including [³H]glycine, [³H]5,7-dichlorokynurenic acid (5,7-DCKA) and [³H]L-689,560 ((±)-4-(<em>trans</em>)-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4-tetrahydroquinoline). Moreover, the potencies of a series of glycine site ligands, including glycine, ACPC, 1-aminocyclobutanecarboxylic acid (ACBC), 5,7-DCKA, 7-chlorokynurenic acid (7-CKA), <em>R</em>(+)-3-amino-1-hydroxy-2-pyrrolidine (HA-966) and <span>D</span>-serine, to inhibit [³H]ACPC binding were highly correlated with their potencies to inhibit [³H]glycine and [³H]5,7-DCKA binding (<em>r</em>²=0.98−0.51). These results demonstrate that [³H]ACPC is a useful tool for examining the neurochemical and pharmacological properties of strychnine-insensitive glycine receptors.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 221-227"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90061-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19692838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}