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

The effect of dopamine D-1 and D-2 receptor stimulation on body temperature has been investigated in male mice. The selective D-2 receptor agonists, quinpirole and LY 163502, and the mixed D-1/D-2 agonist, apomorphine, induced a dose-dependent hypothermia, whereas the selective D-1 receptor agonists, SK&F 81297, SK&F 38393 and SK&F 75670, induced hyperthermia. The hyperthermic responses of these agents were of a similar magnitude although the relative efficacies determined in vitro with the adenylate cyclase assay were different. The peripherally acting D-1 agonist, fenoldopam, did not influence body temperature, indicating that the hyperthermia is mediated, centrally. Studies with combinations of quinpirole and SK&F 38393 showed that the effect of one of the substances could be counteracted by the other. Furthermore, antagonist studies showed that the hypothermia induced by quinpirole could be inhibited by the D-2-selective antagonist, YM 09151-2, and by the mixed D-1/D-2 antagonist, cis(Z)-flupentixol, but not by the D-1-selective antagonist, SCH 23390. Similar results were found for apomorphine-induced hypothermia. SK&F 38393-induced hyperthermia could be antagonized by all three antagonists. These results suggest that the two receptor subtypes act differentially on body temperature, and that they influence a common out-put system, but in opposite directions. These findings are opposite to those of behavioural studies, where a synergistic function of D-1 and D-2 receptors has been demonstrated in the regulation of motor function.
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PMID:The effects of dopamine D-1 and D-2 receptor agonists on body temperature in male mice. 257 99

Stimulation of adenylate cyclase by dopamine in homogenates of the striatum was unaltered in rats which had received either a single or a series of 10 electroconvulsive shock, compared to those which received sham treatment. In homogenates of the limbic forebrain, stimulation by both 100 microM dopamine and by 4 microM SKF 38393 was significantly increased after chronic electroconvulsive shock. The activity of D2 receptors, as measured by inhibition of forskolin-stimulated adenylate cyclase, in the presence of the D1 receptor antagonist SCH 23390, was unaltered by chronic electroconvulsive shock in either area of the brain. The selective effect of chronic electroconvulsive shock in increasing the activity of D1 receptors may account both for the increase, in dopamine-mediated behaviour, seen after chronic electroconvulsive shock and for the antiparkinsonian effects of this treatment.
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PMID:Effects of chronic electroconvulsive shock on D1 and D2 dopamine receptor-mediated activity of adenylate cyclase in homogenates of striatum and limbic forebrain of rat. 267 65

[3H]SCH 23390 binding and dopamine (DA)-stimulated adenylate cyclase activity were measured in brain membrane preparations from rats chronically treated with imipramine (10 mg/kg twice daily for 14 days). [3H]SCH 23390 binding sites were decreased by 27% in the limbic system but only 14% in the striatum. The responsiveness of adenylate cyclase to DA was reduced by 38% in the limbic system but was not modified in the striatum. Concomitant treatment with alpha-methyltyrosine (alpha-MPT) (50 mg/kg daily for 14 days) prevented the imipramine-induced reduction in both [3H]SCH 23390 binding sites and the responsiveness of adenylate cyclase to DA.
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PMID:Chronic imipramine reduces [3H]SCH 23390 binding and DA-sensitive adenylate cyclase in the limbic system. 268 9

1. Dose-dependent vasodilator responses to dopamine, isoprenaline, noradrenaline, 3-isobutyl-1-methylxanthine (IBMX) and sodium nitroprusside were obtained in isolated perfused mesentery preparations, taken from reserpine-treated rats of different ages. The preparations were pretreated with phenoxybenzamine (1 microM) and perfused with physiological salt solution containing cocaine (10 microM), additional KCl (20 mM) and vasopressin (0.1 microM). 2. Vasodilator responses to dopamine were abolished by the dopamine1 (DA1)-selective antagonist SCH 23390 (10 nM) and those to isoprenaline by propranolol (1 microM), but the vasodilator responses to noradrenaline were abolished only when SCH 23390 and propranolol were used together. This indicated that dopamine was acting via DA1-receptors, isoprenaline via beta-adrenoceptors and that noradrenaline could act via DA1-receptors and beta-adrenoceptors in this preparation. 3. Responses to all the vasodilator drugs decreased in magnitude between the ages of 1 and 2 months. Responses to dopamine declined further in 4 month-old rats and were negligible at 6 or 22-24 months of age. Responses to isoprenaline were well maintained up to 6 months of age, but were negligible at 22-24 months. 4. It is concluded that, in the rat mesenteric vasculature, there is a non-specific decline in responses to vasodilator drugs during development (1 to 2 months). Subsequently there is a specific decline in DA1-receptor-mediated and beta-adrenoceptor-mediated responses; the former are lost at an earlier age than the latter. This different time course suggests that age influences receptor numbers, or their coupling to adenylate cyclase, rather than a post-receptor event in the adenylate cyclase/cyclic AMP pathway.
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PMID:Vasodilator responses to dopamine in rat perfused mesentery are age-dependent. 280 50

Adenylate cyclase and guanosine triphosphatase (GTPase) activities in response to dopamine (DA) were determined in membranes prepared from striata of mice treated with haloperidol for a period of 3 months. D1- and D2 receptor-mediated effects were investigated in the presence of 2 microM (-)-sulpiride and 0.1 microM SCH 23390, respectively. The drug treatment produced a 38% increase in the maximal inhibition of adenylate cyclase activity elicited by DA via D2 receptors. D1-mediated stimulation of adenylate cyclase was not affected. The enhanced D2 inhibition of adenylate cyclase was associated with a 45% increase in the stimulatory response of GTPase activity via D2 sites. These results indicate that D2 receptors linked to inhibition of adenylate cyclase and to stimulation of GTPase become supersensitive following in vivo chronic blockade of DA receptors.
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PMID:Supersensitivity of striatal D2 dopamine receptors mediating inhibition of adenylate cyclase and stimulation of guanosine triphosphatase following chronic administration of haloperidol in mice. 281 91

In synaptic plasma membranes of rat striatum, activation of dopamine receptors stimulates a high affinity GTPase activity. The rank order of potency of various dopamine receptor agonists in increasing GTP hydrolysis is the following: (-)-propylnorapomorphine greater than (-)-apomorphine = (+/-)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene [(+/-)-A-6,7-DTN] greater than dopamine = LY 171555 greater than noradrenaline. The selective D-1 dopamine receptor agonist, SKF 38393, does not produce a significant increase in GTP hydrolysis. Moreover, the dopamine-stimulated GTPase activity is completely reversed by the D-2 receptor antagonists, 1-sulpiride and zetidoline, but not by the selective D-1 antagonist SCH 23390. Na+ modulates the dopamine receptor-regulated GTP hydrolysis by increasing the percentage of stimulation and decreasing the agonist potency. Intrastriatal injection of pertussis toxin, which impairs the function of the inhibitory guanine nucleotide binding regulatory protein (Ni) of adenylate cyclase, significantly reduces the dopamine stimulation of striatal GTPase activity and the dopamine inhibition of adenylate cyclase. In contrast, cholera toxin, which blocks the stimulation of GTPase activity by hormones which increase adenylate cyclase activity, does not modify the dopamine-stimulated GTPase activity. These data indicate that the stimulation of GTPase activity elicited by dopamine results from activation of the D-2 type of dopamine receptors and is expression of the increased turnover of GTP at the level of Ni. The results are consistent with the idea that Ni is involved in the inhibitory coupling of striatal D-2 receptors to adenylate cyclase.
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PMID:Pharmacological and biochemical characterization of dopamine receptors mediating stimulation of a high affinity GTPase in rat striatum. 282 Apr 23

Dopamine is able to inhibit the epinephrine-induced aggregation of human blood platelets, but the mechanism of action has not been elucidated. In this study we report that membranes from human blood platelets possess high affinity, saturable and stereoselective binding sites for the D1 dopamine receptor antagonist (3H) SCH 23390. (3H) SCH 23390 appeared to label a single class of binding sites with a Bmax of 18.6 +/- 1.6 fmol/mg protein and a KD of 0.8 nM. The potencies of different dopaminergic antagonists and agonists in displacing (3H) SCH 23390 from blood platelet membranes were similar to those obtained for striatal membranes. Unlike the classically defined D1 receptors, e.g. those in striatum, the D1 receptor sites on platelets appeared not to be coupled to the adenylate cyclase system, hence the term "D1-like". The D1 agonist SKF 38393 was more potent than dopamine in inhibiting platelet aggregation induced by epinephrine, and the effects of dopamine and SKF 38393 were prevented by SCH 23390. These results suggest that the inhibitory action of dopamine on the epinephrine-induced platelet aggregation is mediated through these D1-like receptors.
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PMID:Identification of D1-like dopamine receptors on human blood platelets. 283 19

Incubation of cultured mesenteric vascular smooth muscle cells with dopamine, in the presence of propranolol, caused an increase in cyclic AMP formation in a concentration-dependent manner (Ka apparent 6.8 +/- 0.5 microM). This effect of dopamine was inhibited by the DA1-receptor antagonist SCH 23390 (Ki = 1 nM). These results suggest that cultured mesenteric vascular smooth muscle cells express DA1-receptors linked to adenylate cyclase.
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PMID:Cultured mesenteric vascular smooth muscle cells express dopamine DA1-receptors. 285 67

The effect of octopamine on intestinal smooth muscle of rabbit isolated jejunum has been studied. Octopamine induced a dose-dependent decrease of muscle tone and this reproducible relaxation was not modified by tetrodotoxin or by agents that acted on adrenergic nerve terminals. Adrenoceptor antagonists, at concentrations sufficient to block each adrenoceptor type, did not reduce the actions of octopamine. On the other hand, octopamine-induced relaxations were affected by agents that have the ability to change cyclic AMP (cAMP) content; such as alloxan (an adenylate cyclase inhibitor), imidazole (a stimulator of phosphodiesterase), and isobutyl methylxanthine (an inhibitor of phosphodiesterase). Direct stimulation of adenylate cyclase by octopamine was demonstrated using radioimmunoassay of cAMP. Furthermore, haloperidol and perphenazine at concentration required to block dopamine receptor sites attenuated both smooth muscle relaxation and the formation of cAMP induced by octopamine. The effect of octopamine was totally blocked by SCH 23390, an antagonist of dopamine D-1 receptors. The lack of effect of domperidone and sulpiride, antagonists of dopamine D-2 receptors, on the actions of octopamine excludes the involvement of dopamine D-2 receptors. These results suggest that octopamine acts on intestinal dopamine D-1 receptor sites to produce relaxation of rabbit jejunum through an increase of cAMP.
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PMID:Octopamine relaxes rabbit jejunal smooth muscle by selective activation of dopamine D1 receptors. 285 5

Fenoldopam (SKF 82526), a dopamine agonist which exhibits D-1 receptor subtype selectivity, was evaluated as a radioligand for this receptor subtype. In saturation studies in rat striatal membrane preparations, [3H]-fenoldopam appeared to label a single binding site with a KD of 2.3 +/- 0.1 nM and a Bmax of 590 +/- 40 fmoles/mg protein. In competition binding experiments, binding was shown to be stereoselective, and rank ordering of affinities of dopaminergic and non-dopaminergic compounds closely correlated with potencies of these compounds in stimulating or inhibiting dopamine-sensitive adenylate cyclase (D-1) and in binding to D-1 sites labelled with the antagonist [3H]-cis-flupenthixol. The most potent competitors were the recently identified D-1 selective antagonists, SCH 23390 and SKF R-83566. [3H]-Fenoldopam was also used to assess agonist/D-1 receptor interactions. The results suggest that [3H]-fenoldopam is a useful and selective agonist radioligand for the D-1 receptor.
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PMID:Binding of a novel dopaminergic agonist radioligand [3H]-fenoldopam (SKF 82526) to D-1 receptors in rat striatum. 285 1


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