Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The localization of neuroleptic receptors was studied in the caudate-putamen (CP) and the zona compacta of the substantia nigra using light microscopic autoradiography of 3H-spiperone binding sites. Lesion of the dopaminergic input to the caudate-putamen produced an increase in receptors in the CP, possibly reflecting denervation supersensitivity. Kainic acid lesions and decortication produced significant decreases of 61% and 18% in striatal receptors. This suggests that in the caudate-putamen most of the dopamine receptors are on intrastriatal neurons, but some are also localized to the afferents from the cortex. Lesion of the nigro-striatal dopaminergic pathway produced a large (48%) decrease in receptor sites in the substantia nigra zona compacta while kainic acid intrastrially and striato-nigral pathway lesions had no significant effect. These results suggest that the majority of dopamine receptors in the zona compacta which bind neuroleptics are located on cell bodies and processes of dopaminergic neurons and are anatomically distinct from dopamine-stimulated adenylate cyclase sites.
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PMID:Autoradiographic localization of neuroleptic and dopamine receptors in the caudate-putamen and substantia nigra: effects of lesions. 4 60

The topographical distribution of a cAMP-regulated phosphoprotein of an apparent molecular weight (Mr) of 32,000 (32K) was examined in homogenates prepared from microdiscs punched out from serial frozen slices of the striatum. The amount of this phosphoprotein progressively diminished from the rostral to the caudal part of the striatum as did both the dopamine-innervation and the dopamine (D1)-sensitive adenylate cyclase. After kainic acid lesion of the rostral part of the striatum, the 32K phosphoprotein disappeared in this area and we observed a 48% decrease in the amount of 32K phosphoprotein found in the substantia nigra. 6-Hydroxydopamine lesions of the nigro-striatal dopaminergic pathway did not affect the 32K phosphoprotein either in striatum or substantia nigra. These results suggest that in the nigro-striatal pathway, the 32K phosphoprotein is closely associated with dopaminoceptive neurons containing D1 receptors. In the cerebral cortex the association of 32K phosphoprotein with dopaminoceptive neurons is more questionable since we did not find a higher density of this phosphoprotein in areas containing a high amount of D1 receptor (frontal cerebral cortex) than in areas containing a low amount of D1 receptor (parietal cerebral cortex). In the course of this study we found another cAMP-regulated phosphoprotein of an Mr of 48,000 (48K). The amount of this phosphoprotein increased progressively from the rostral to the caudal part of the striatum, a pattern of distribution close to that of serotonin terminals. This protein was also present in the substantia nigra. Kainic acid lesioning of the rostral part of the striatum did not affect the amount of the 48K phosphoprotein within the substantia nigra.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Topographical distributions of 32K and 48K cAMP-regulated phosphoproteins: relationships to dopamine and serotonin innervations in striatum, substantia nigra and cerebral cortex. 609 35

Kainic acid lesion of rat striata reduces the specific dopamine receptor binding of the butyrophenone antagonist [3H]spiperone and the butyrophenone-like antagonist [3H]domperidone by 56% and 59% respectively. Significantly greater decreases in binding were observed with the agonist [3H]N-propylnorapomorphine (NPA) and the antagonist [3H]flupentixol which showed 79% and 73% losses of high affinity binding respectively. These data indicate that, in part, [3H]spiperone and [3H]domperidone label distinct dopamine receptors with different neuronal localizations from those labeled by [3H]flupentixol and [3H]NPA. Our data is consistent with the hypothesis that [3H]flupentixol and [3H]NPA bind preferentially to adenylate cyclase-linked dopamine (D1) receptors.
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PMID:Kainate lesion dissociates striatal dopamine receptor radioligand binding sites. 721 42