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)

NPS(o-nitrophenyl sulfenyl)-ACTH stimulated steroidogenesis in Y1 cells to the same maximum level as did ACTH, but with a 60-fold lower potency than the native hormone. NPS-ACTH also stimulated the extracellular accumulation of cAMP in Y1 cells with lower potency than the unmodified hormone. The amount of cAMP accumulated in the presence of NPS-ACTH approached 75% of the maximum with ACTH. In Y1 plasma membranes, NPS-ACTH was a partial agonist of adenylate cyclase activity, witn an efficacy dependent upon the type of guanyl nucleotide present. The steroidogenic responses of two Y1(Kin) mutants and two Y1(Cyc) mutants to NPS-ACTH paralleled their responses to ACTH and reflected closely their defects in cAMP-dependent protein kinase and ACTH-sensitive adenylate cyclase activity. These data imply an obligatory role for adenylate cyclase and cAMP-dependent protein kinase activities in stimulation of steroidogenesis in Y1 cells by NPA-ACTH.
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PMID:Responses of Y1 adrenocortical tumor cells to o-nitrophenyl sulfenyl ACTH. 624 80

Rats received therapeutically equivalent doses of either haloperidol (1.7-1.9 mg/kg/day), sulpiride (112-116 mg/kg/day) or clozapine 30-35 mg/kg/day) continuously for 4 weeks. Treatment with haloperidol, but not sulpiride or clozapine, caused inhibition of stereotyped behaviour induced by apomorphine (0.125-0.25 mg/kg SC). Following drug withdrawal for up to 7 days, haloperidol and sulpiride, but not clozapine treatment caused an exaggeration of stereotyped behaviour induced by apomorphine. Bmax values for striatal 3H-spiperone binding were elevated in animals treated for 2 and 4 weeks with haloperidol, but not with sulpiride or clozapine. Following drug withdrawal, haloperidol, but not sulpiride or clozapine, treatment caused an increase in Bmax for striatal 3H-spiperone binding. Bmax values for striatal 3H-NPA binding revealed no change during haloperidol or clozapine treatment. Sulpiride treatment for 1 week caused an increase in Bmax for 3H-NPA binding, which returned to control levels at 2 and 4 weeks. Following drug withdrawal, there was an increase in Bmax for 3H-NPA binding in rats treated with haloperidol and sulpiride, but not clozapine. On continuous treatment and following withdrawal from haloperidol, sulpiride, or clozapine the ability of dopamine to stimulate striatal adenylate cyclase activity did not differ from that in control animals. Repeated administration of sulpiride or clozapine may not induce striatal dopamine receptor supersensitivity when given in clinically relevant doses, although haloperidol does.
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PMID:Differential alterations in striatal dopamine receptor sensitivity induced by repeated administration of clinically equivalent doses of haloperidol, sulpiride or clozapine in rats. 644 52

(-)-2,10,11-Trihydroxy-N-n-propylnoraporphine (TNPA,2c) has been synthesized from thebaine (3a), via northebaine (3b), normorphothebaine (2a), and alkylation to the N-propyl derivative 2b. O-Demethylation gave the desired product 2c. Compound 2c showed activity comparable to its 10,11-dihyroxy counterpart (NPA, 1b) on the stimulation of dopamine-sensitive adenylate cyclase in carp retinal homogenates. The evaluation of 2c on audiogenic seizures in mice, in the protection against paroxysimal EEG and myoclonic response to photic stimulation in the baboon, revealed a similar pharmacological profile in comparison to NPA and apomorphine, with TNPA showing a prolonged duration of action in abolishing myoclonic response to photic stimulation in the baboon.
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PMID:Aporphines. 34. (-)-2,10,11-Trihydroxy-N-n-propylnoraporphine, a novel dopaminergic aporphine alkaloid with anticonvulsant activity. 727 2

We previously reported that dopamine (DA) acted via D2-dopamine receptors on human trophoblastic cells to inhibit basal and hormone-stimulated secretion of human placental lactogen (hPL). We also described that these DA effects were coupled with inhibition of calcium influx. The present study examines the interaction of placental D2-dopamine receptor with adenylate cyclase (AC). Incubations of isolated human term trophoblastic cells with R(-)-propylapomorphine (NPA), (+/-)-PPHT, and bromocriptine (3 different D2 agonists) led to time- and dose-dependent inhibitions of cAMP production as determined by measuring the conversion of [2-3H]-ATP into [2-3H]-cAMP. The maximal inhibition was reached after 15 min of incubation and was 33 +/- 1 (SE) %, 29 +/- 3% and 31 +/- 1% for bromocriptine (10(-5) M), NPA (10(-7) M) and (+/-)-PPHT (10(-8) M) respectively. However, the time- and dose-dependent curves were biphasic with NPA and (+/-)-PPHT and the inhibition of cAMP production was abolished at higher agonist concentrations or after time incubations longer than 15 min. These inhibitions were receptor specific since they were reversed by spiperone and haloperidol, two specific--dopamine antagonist, and by butaclamol (mix D2/D1-dopamine antagonists) but not by alpha- and beta-adrenergic, D1- and D4-dopaminergic, and 5-HT2-serotonergic antagonists. The results reported here suggest that human placental D2 receptors interact with AC to inhibit its activity. Also, bromocriptine seems a better agonist for the characterization of dopaminergic effects on human placenta.
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PMID:D2-dopamine agonists inhibit adenosine 3':5'-cyclic monophosphate (cAMP) production in human term trophoblastic cells. 796 25


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