Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low-affinity (micromolar) 3H-dopamine binding was measured under conditions which permitted dopamine activation and opiate inhibition of adenylate cyclase in rat striatal membranes. Opiate drugs and peptides inhibited the dopamine binding in the presence of both GTP and Gpp(NH)p. Opiate inhibition of adenylate cyclase was, however, observed only in the presence of GTP. It is suggested that the dopamine D1 receptor in striatum may be modulated by the opiate delta receptor through a shared guanine nucleotide binding subunit.
...
PMID:Inhibition of dopamine-activated adenylate cyclase and dopamine binding by opiate receptors in rat striatum. 630 92

A novel benzazepine, SCH 23390, has recently been described as a very potent and selective dopamine D-1 receptor antagonist based on its potent inhibition of dopamine sensitive adenylate cyclase and its selective displacement of 3H-piflutixol from rat striatal receptor sites. In the present study, the in vitro binding of 3H-SCH 23390 to specific striatal receptor sites has been characterized. Binding was saturable and stereospecific, and the results of both saturation and competition studies are consistent with the binding of 3H-SCH 23390 to a single striatal site. A KD of 0.53 nM was obtained through Scatchard analysis. Relative potencies of a variety of neuroleptics in competing with 3H-SCH 23390 and also 3H-spiperone support an interpretation that the single site to which 3H-SCH 23390 binds is the D-1 dopamine receptor. Also, the binding capacity of 3H-SCH 23390 (69 pmoles/gm wet weight) is in agreement with published values for the binding capacities of 3H-piflutixol and 3H-flupentixol. These data, coupled with the low level of non-specific binding encountered with this radioligand (4-8% of total binding at normally employed ligand concentration of 0.3 nM), its high specific activity and its negligible binding to plastic and glass surfaces make it ideally suited for studying interactions with this receptor.
...
PMID:Characterization of the binding of 3H-SCH 23390, a selective D-1 receptor antagonist ligand, in rat striatum. 638 55

Prolonged incubation of slices of striatum with agonists of D-1 dopamine receptors increased phosphorylation of at least 5 membrane protein bands. The extent of the increase in phosphate-incorporation depended on the concentration (10(-5) M-10(-4) M) of the agonist in the incubation medium and the duration of incubation (20 min or longer). Preincubation of slices with haloperidol (10(-6) M) greatly reduced, while (-)sulpiride (10(-6) M) failed to alter the increase of phosphorylation elicited by dopamine. Prolonged incubation of striatal slices with LY 141865 (10(-5) M) or isoproterenol (10(-5) M) increased the phosphate-incorporation only in one of the protein bands with an apparent molecular weight of 42,000. Incubation of striatal slices with cholera toxin increased the phosphorylation of protein bands in a similar way to those elicited by dopamine. The present results suggest that the increased phosphorylation of certain protein bands elicited by prolonged exposure of striatal slices to D-1 dopamine receptor agonists may be associated with the desensitization of dopamine-sensitive adenylate cyclase.
...
PMID:Phosphorylation of membrane proteins in response to persistent stimulation of adenylate cyclase-linked dopamine receptors in slices of striatum. 672 31

When rat striatal membranes, photolabeled with [3H]dopamine under assay conditions similar to those used for dopamine-sensitive adenylate cyclase, were subjected to sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, several radioactively labeled bands appeared. Labeling of these bands was reduced in the presence of non-radioactive dopamine during photolysis, but was unaffected by the presence of sulpiride. Haloperidol preferentially reduced the labeling of the main band which had a molecular weight of about 57,000 rather than the other weakly labeled bands. Labeling of this 57,000 dalton protein was not apparent when rat cerebellar membranes were used and was markedly eliminated by kainic acid-induced lesions that destroyed the intrastriatal nerve cell bodies. These results indicate that this 57,000 dalton protein is the binding subunit of the D-1 dopamine receptor.
...
PMID:Identification of the D-1 dopamine receptor subunit in rat striatum after photoaffinity labeling. 731 90

Three genomic clones encoding dopamine D1-like receptors were isolated from the avian species Gallus domesticus. Two of these genes encode proteins of 451 and 488 amino acids, which, based on deduced amino acid sequence identity and homology of exhibited pharmacological profiles, appear to be species homologs of mammalian and vertebrate D1/D1A and D5/D1B receptors, respectively. The third genomic clone, termed D1D, encodes a protein of 445 amino acids displaying a deduced amino acid sequence identity within putative transmembrane domains of 75% to mammalian D1/D1A and 77% to D5/D1B receptors with overall sequence homologies of only 49% and 46%, respectively. Membranes from COS-7 cells transfected with D1D DNA bound [3H]SCH-23390 in a saturable manner with high affinity (approximately 300 pM) and with a pharmacological profile clearly indicative of a dopamine D1-like receptor. The D1D receptor exhibited affinities for 6,7-dihydroxy-2-aminotetralin and dopamine 10-fold higher than D1/D1A receptors, characteristic of the D5/D1B receptor subfamily. In contrast, the D1D receptor bound dopaminergic agents, such as SKF-38393, apomorphine, pergolide, and lisuride, with affinities 10-fold higher than other cloned mammalian or vertebrate D1A/D1B receptor subtypes, while both clozapine and haloperidol displayed considerably lower affinity for the D1D receptor. Based on the low overall amino acid sequence identity (54%) and unique pharmacological profile, the avian dopamine D1D receptor does not appear to be a species homolog of the recently cloned vertebrate D1C receptor (Sugamori, K.S., Demchyshyn, L. L., Chung, M., and Niznik, H. B. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 10536-10540). As with all cloned mammalian and vertebrate D1-like receptors, the D1D receptor stimulates adenylate cyclase activity in the presence of dopamine or SKF-82526. Northern blot analysis reveals the selective expression of both avian D1D and D1A receptor mRNAs only in brain with the D1B receptor more widely distributed and localized in tissues such as brain, kidney, and spleen. The isolation of four distinct vertebrate dopamine D1 receptor subtypes suggests the existence of additional mammalian D1 like receptor genes that may account for the observed pharmacological and biochemical multiplicity of dopamine D1-like receptor mediated events.
...
PMID:The dopamine D1D receptor. Cloning and characterization of three pharmacologically distinct D1-like receptors from Gallus domesticus. 787 48

Although partial efficacy dopamine D1 receptor agonists have little therapeutic benefit in parkinsonism, the first high potency, full efficacy dopamine D1 receptor agonist dihydrexidine recently has been shown to have profound antiparkinsonian effects. One reason for the greater antiparkinsonian effects of dihydrexidine vs. SKF38393 might be that SKF38393, while a partial dopamine D1 receptor agonist in rodent striatal preparations, has virtually no agonist activity in monkey striatum (Pifl et al., 1991, Eur. J. Pharmacol. 202, 273). To explore this hypothesis, we compared the dopamine D1 receptor affinity and efficacy of dihydrexidine and SKF38393 in striatum from rat and monkey. In vitro binding studies using membranes from putamen of adult rhesus monkeys demonstrated that dihydrexidine competed for dopamine D1 receptors (labeled with [3H]SCH23390) with high potency (IC50 = 20 nM vs. ca. 10 nM in rat brain). SKF38393 was about 4-fold less potent than dihydrexidine in both monkey and rat brain. The in vitro functional activity of these drugs was assessed by their ability to stimulate adenylate cyclase activity in tissue homogenates. Dihydrexidine was of full efficacy (relative to dopamine) in stimulating cAMP synthesis in both monkey and rat. SKF38393 was only a partial efficacy agonist in both rat striatum and monkey putamen, but contrary to the original hypothesis, it had the same efficacy (ca. 40% relative to dihydrexidine) in membranes from both species. Interestingly, greater between-subject variation was found in the stimulation produced by SKF38393 in primate compared to rat brain, although the basis for this variation is unclear.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Dopamine D1 receptors: efficacy of full (dihydrexidine) vs. partial (SKF38393) agonists in primates vs. rodents. 790 11

Repeated, once daily morphine treatment (14 days) as well as chronic morphine administration (6 days) caused a rebound reduction in the electrically evoked release of [3H]dopamine from superfused rat striatal slices 1 day after the last subcutaneous injection. Interestingly, whereas [3H]dopamine release remained significantly reduced for at least 3 weeks following morphine withdrawal in chronically treated (tolerant/dependent) rats, neurotransmitter release from dopaminergic nerve terminals gradually increased above control values following cessation of repeated morphine administration. Postsynaptically, dopamine D1 receptor-stimulated adenylate cyclase appeared to be sensitized 1-3 days but was unchanged 3 weeks after chronic morphine treatment. In contrast, such an enhanced postsynaptic dopamine D1 receptor efficacy did not occur 1-3 days following repeated morphine administration, but appeared to develop slowly resulting in a profound increase of dopamine-sensitive adenylate cyclase 3 weeks after the last injection. The inhibitory effect of dynorphin A-(1-13) on [3H]dopamine release, as well as that of [Met5]enkephalin on dopamine D1 receptor-stimulated adenylate cyclase appeared to be unchanged subsequent to repeated or chronic morphine treatment. These data indicate that, long after cessation of drug treatment, chronic morphine treatment causes a reduction whereas repeated morphine administration gradually induces an enhancement of opioid receptor-regulated dopaminergic neurotransmission due to local adaptive changes within the rat striatum. Such distinct long-lasting alterations of dopaminergic neurotransmission induced by different temporal patterns of morphine administration in projection areas of mesencephalic dopaminergic neurons may be related to the enduring effects of drug abuse such as behavioural sensitization and drug craving.
...
PMID:Repeated and chronic morphine administration causes differential long-lasting changes in dopaminergic neurotransmission in rat striatum without changing its delta- and kappa-opioid receptor regulation. 790 81

Receptors for dopamine are present on horizontal cells of fish retina that are linked to the activation of adenylate cyclase. In the present study, the goldfish (Carassius auratus) gene that encodes these receptors, referred to as gfD1, was isolated and analyzed. A single open reading frame within the gfD1 gene encodes a protein of 363 amino acids that is highly homologous with dopamine D1 receptors from rats and humans. Interestingly, the carboxyl terminus of gfD1 lacks 80 amino acids that are present in the mammalian receptor sequences. RNA analysis using the polymerase chain reaction demonstrated that the gene is expressed in the goldfish retina and is intronless within the coding region. The fact that gfD1 encodes a dopamine D1 receptor was demonstrated through pharmacological analysis of transfected cells. Both the gfD1 receptor and the human D1 receptor expressed in mammalian cells had high affinity for SCH-23390 and other D1-specific ligands. In addition, the gfD1 receptor and the human D1 receptor were able to stimulate the accumulation of cAMP in response to SKF-38393 or dopamine. Interestingly, stimulation of both the gfD1 and human receptors with dopamine also resulted in an increase in intracellular Ca2+. Finally, long term pretreatment of transfected cells with dopamine resulted in the desensitization and down-regulation of both the goldfish and human receptors.
...
PMID:Cloning and characterization of a truncated dopamine D1 receptor from goldfish retina: stimulation of cyclic AMP production and calcium mobilization. 826 47

Coated vesicles (CVs) isolated from bovine striatal tissue were examined to determine whether they are associated with dopamine signal systems consisting of dopamine D1 and D2 receptors, G proteins, and adenylate cyclase. Dopamine receptors in CVs were characterized by a dopamine D1 receptor antagonist, [3H]SCH 23390, and a dopamine D2 receptor antagonist, [3H]-spiroperidol. The bindings of both ligands were specifically saturable and reversible with a dissociation constant (KD) of 0.65 and 0.5 nM, respectively. Dopaminergic antagonists and agonists inhibited the specific bindings of [3H]SCH 23390 and [3H]spiroperidol in a stereoselective and concentration-dependent manner with an appropriate rank order potency for dopamine D1 or D2 receptors. The regulations of the agonist binding by guanyl-5-ylimidodiphosphate were observed. ADP ribosylation of the CVs with [32P]NAD demonstrated predominant labeling of bands of M(r) 47,000-52,000, 42,000-45,000, and 40,000-39,000, which corresponded to the known molecular weights of the alpha subunits of Gs and Gi proteins. The presence of alpha and beta subunits of G proteins in the CVs was also confirmed by immunoblotting assay. Adenylate cyclase activity, which was stimulated by SKF 38393 and inhibited by dopamine D2 receptor agonists, was present in the CVs. These findings suggest that the dopamine D1 and D2 receptors in the CVs couple with adenylate cyclase via Gs/Gi protein.
...
PMID:Dopamine D1 and D2 receptors and their signal system present in coated vesicles prepared from bovine striatal tissue. 829 21

Morphological transformation of Chinese hamster ovary (CHO) cells can be induced by exogenous addition of cyclic AMP (cAMP) or through the stimulation of G protein-coupled receptors ectopically expressed in these cells. The morphological transformation has been shown to represent a phenotypic suppression of CHO cell tumorigenic potential. Studies were undertaken to determine which receptor-activated signal transduction pathway initiates the progression from a tumorigenic to a non-tumorigenic phenotype. Stimulation of CHO cells expressing the dopamine D1 receptor (CHOD1) with a D1 selective agonist, SKF38393, resulted in an increase in cAMP accumulation which correlated with morphologic transformation. SKF38393 had no effect on intracellular calcium levels, arguing against a requirement for phospholipase C or calcium mobilization in the D1-stimulated morphology change. In contrast, stimulation of muscarinic m5 (CHOm5) or vasopressin V1a (CHOV1a) receptors expressed in CHO cells with carbachol or arginine vasopressin (AVP), respectively, did not result in an increase in intracellular calcium and a morphology change. The time course of carbachol-stimulated calcium influx correlated with the time course of morphological transformation, but not with carbachol-stimulated cAMP or inositol, 1,4,5-trisphosphate (IP3) accumulation. Furthermore, no increase in cAMP accumulation was observed in AVP-stimulated CHOV1a cells, suggesting a cAMP-independent stimulation of the transformation process. Carbachol-stimulated CHO cells expressing the m2 muscarinic receptor (CHOm2) failed to undergo a morphological transformation, yet released IP3. Therefore, phospholipase C-mediated signal transduction is not sufficient for the morphological transformation of CHO cells. It appears that receptor-stimulated morphologic transformation of CHO cells can be induced via two independent signaling pathways, mediated by adenylate cyclase or receptor-operated calcium channels.
...
PMID:Independent induction of morphological transformation of CHO cells by receptor-activated cyclic AMP synthesis or by receptor-operated calcium influx. 861 96


<< Previous 1 2 3 4 Next >>

---