Studies on the use of a novel affinity matrix, sepharose amine-succinyl-amine haloperidol hemisuccinate, ASA-HHS, for purification of canine dopamine (D2) receptor

Antonian, Lida; Antonian, Edna; Murphy, Randall B.; Schuster, David I.

doi:10.1016/0024-3205(86)90140-2

Cited by 14 publications

(2 citation statements)

References 23 publications

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“…Dehydroxyaminohaloperidol-sepharose ........ Chan and Madras (1983) Haloperidol hemisuccinate-sepharose ....... ..... ................ Antonian et al (1986) Haloperidol-sepharose .. ... Ramwani and Mishra (1986) (Carboxymethy1ene)oximinospiperone-sepharose ....... .. Senogles et al (1986) Clebopride(ally1oxy)-sepharose .... ... Niznik et al (1986) Possible abnormal functional states of the Dz receptor Of the two affinity states in which Dz can exist (see Fig. 4), it is the high-affinity state which is functional in the anterior pituitary gland Mc-Donald et al, 1984).…”

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confidence: 99%

Dopamine receptors and the dopamine hypothesis of schizophrenia

Seeman

1987

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The discovery of neuroleptic drugs in 1952 provided a new strategy for seeking a biological basis of schizophrenia. This entailed a search for a primary site of neuroleptic action. The Parkinsonian effects caused by neuroleptics suggested that dopamine transmission may be disrupted by these drugs. In 1963 it was proposed that neuroleptics blocked "monoamine receptors" or impeded the release of monoamine metabolites. The neuroleptic concentration in plasma water or cerebrospinal fluid was of the order of 2 nM for haloperidol in clinical therapy. A systematic research was made between 1963 and 1974 for a primary site of neuroleptic action which would be sensitive to 2 nM haloperidol and stereoselective for (+)-butaclamol. Direct evidence that neuroleptics selectively blocked dopamine receptors occurred in 1974 with the finding that nanomolar concentrations of these drugs stereoselectively inhibited the binding of [3H]-dopamine or [3H]-haloperidol. These binding sites, now termed D2 dopamine receptors (which inhibit adenylate cyclase), are blocked by neuroleptics in direct relation to the antipsychotic potencies of the neuroleptics. No such correlation exists for D1 receptors (which stimulate adenylate cyclase). Based on the fact that dopamine-mimetic drugs elicited hallucinations, and that neuroleptics caused rigidity, Van Rossum in 1966 had suggested a hypothesis that dopamine pathways may be overactive in schizophrenia. The D2-selective blockade by all neuroleptics (except the monoamine-depleting reserpine) provided strong support for the dopamine hypothesis. Further support now comes from postmortem data and in vivo positron tomographic data, both of which indicate that the density of D2 receptors are elevated in the schizophrenic brain. The postmortem data indicate a bimodal pattern with half the schizophrenics having striatal D2 densities of 14 pmol/g (control is 13 pmol/g) and the other half having 26 pmol/g. Current positron tomographic data indicate D2 densities of 14 pmol/g in control subjects, but values of 34 pmol/g in drug-naive schizophrenics. Future tests of the dopamine hypothesis of schizophrenia may entail an examination of the amino acid composition and genes for D2 receptors in schizophrenic tissue, an examination of the ability of the D2 receptor to become phosphorylated and to desensitize into the low-affinity state, and an examination of the interaction of D2 receptors with D1 receptors or other neurotransmitters.

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Section: :Manmentioning

confidence: 99%

Dopamine receptors and the dopamine hypothesis of schizophrenia

Seeman

1987

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383

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“…Affinity resins based on various dopaminergic antagonists were prepared and employed for partial purification of the D2 doparnine receptor (Antonian et al, 1986;Ramwani and Mishra, 1986;Senogles et al, 1986). Recently, the D2 receptor was purified to homogeneity from bovine striatum (Elazar et al, 1988a;Williamson et al, 1988) and from bovine anterior pi-tuitary (Senogles et al, 1988).…”

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Phosphorylation by Cyclic AMP‐Dependent Protein Kinase Modulates Agonist Binding to the D₂ Dopamine Receptor

Elazar¹,

Fuchs²

1991

Journal of Neurochemistry

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Phosphorylation of striatal membranes by cyclic AMP-dependent protein kinase resulted in a reduction in the affinity of the D2 dopamine receptor toward its agonist N-propylnorapomorphine while the affinity to D2-specific antagonists remained unchanted. The inhibitory effects observed by phosphorylation and guanine nucleotides on agonist binding to the D2 receptor were additive. The purified D2 dopamine receptor from bovine striatum was specifically phosphorylated by cyclic AMP-dependent protein kinase with an apparent stoichiometry of 0.7 mol phosphate/mol receptor. The phosphorylated purified D2 receptor also exhibited a reduced agonist binding activity with no change in antagonist binding. The action of cyclic AMP-dependent protein kinase on both the membrane preparation and the purified D2 receptor was inhibited by a specific inhibitor of the kinase. These data indicate that phosphorylation mediated by cyclic AMP-dependent protein kinase may represent a physiological pathway for modulation of the receptor binding activity.

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Purification of brain D2 dopamine receptor.

et al. 1988

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D2 dopamine receptors have been extracted from bovine brain using the detergent cholate and purified approximately 20,000‐fold by affinity chromatography on haloperidol‐sepharose and wheat germ agglutinin‐agarose columns. The purified preparation contains D2 dopamine receptors as judged by the pharmacological specificity of [3H]spiperone binding to the purified material. The sp. act. of [3H]spiperone binding in the purified preparation is 2.5 nmol/mg protein. The purified preparation shows a major diffuse band at Mr 95,000 upon SDS‐polyacrylamide gel electrophoresis and there is evidence for microheterogeneity either at the protein or glycosylation level. Photoaffinity labelling of D2 dopamine receptors also shows a species of Mr 95,000. The D2 dopamine receptor therefore is a glycoprotein of Mr 95,000.

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Studies on the use of a novel affinity matrix, sepharose amine-succinyl-amine haloperidol hemisuccinate, ASA-HHS, for purification of canine dopamine (D2) receptor

Cited by 14 publications

References 23 publications

Dopamine receptors and the dopamine hypothesis of schizophrenia

Dopamine receptors and the dopamine hypothesis of schizophrenia

Phosphorylation by Cyclic AMP‐Dependent Protein Kinase Modulates Agonist Binding to the D₂ Dopamine Receptor

Purification of brain D2 dopamine receptor.

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Studies on the use of a novel affinity matrix, sepharose amine-succinyl-amine haloperidol hemisuccinate, ASA-HHS, for purification of canine dopamine (D2) receptor

Cited by 14 publications

References 23 publications

Dopamine receptors and the dopamine hypothesis of schizophrenia

Dopamine receptors and the dopamine hypothesis of schizophrenia

Phosphorylation by Cyclic AMP‐Dependent Protein Kinase Modulates Agonist Binding to the D2 Dopamine Receptor

Purification of brain D2 dopamine receptor.

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Product

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Phosphorylation by Cyclic AMP‐Dependent Protein Kinase Modulates Agonist Binding to the D₂ Dopamine Receptor