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)

Clonazepam at two doses of 1 mg/kg i.p. significantly decreased 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) contents in the rat caudatus and cortex but not so in the olfactory tubercle, septum and hypothalamus. The drug decreased dopamine (DA) turnover rate in the caudatus, but did not inhibit tyrosine hydroxylase activity. The drug significantly enhanced stereotyped behavior induced by apomorphine and d-methamphetamine. Clonazepam enhanced apomorphine-induced decrease in striatal HVA, and cortical DOPAC and HVA contents, and d-methamphetamine-induced decrease in cortical DOPAC content. Reserpine pretreatment did not affect apomorphine-induced stereotypy and its enhancement with clonazepam. The drug did not activate adenylate cyclase nor DA-sensitive adenylate cyclase in the striatal homogenates and did not change cyclic AMP content in the caudatus. The drug inhibited phosphodiesterase activity in caudate and cortical homogenates but not in vivo. Clonazepam did not alter ChAc and AChE activities in the caudatus, 6 other cerebral regions and the spinal area. Clonazepam also decreased NE turnover in the caudatus and 5-HIAA contents in the brainstem area. These neurochemical and behavioral effects of clonazepam indicate probable postjunctional DA stimulation in the striatum and cortex of the type not linked with adenylate cyclase and phosphodiesterase but probably due to activation of inhibitory gamma-amino butyric acid (GABA) neurons on the strio-nigral pathway.
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PMID:[Influence of clonazepam, an anticonvulsant benzodiazepine drug, on the rat brain monoamine containing neurons especially on dopaminergic neurons (author's transl)]. 20 28

Recent studies have demonstrated that chronic stress increases the firing rate and expression of tyrosine hydroxylase (TH) in neurons of the locus coeruleus (LC), the major noradrenergic nucleus in brain. The present study was undertaken to examine the influence of chronic stress and other treatments known to influence the activity of LC neurons on the cyclic AMP (cAMP) second messenger system in these neurons. Chronic (5 days) cold exposure significantly increased levels of TH immunoreactivity in the LC, as previously reported, but not in substantia nigra (SN) or ventral tegmentum (VT), two dopaminergic nuclei studied for comparison. Chronic cold exposure increased levels of cAMP-dependent protein kinase activity in soluble, but not particulate, fractions of the LC, and increased basal and GTP- and forskolin-stimulated adenylate cyclase activity in this brain region. In contrast, levels of the protein kinase and adenylate cyclase in VT, SN, and frontal cortex were not significantly influenced by cold exposure. To study further the relationship between regulation of LC firing rate, TH expression, and the cAMP system in the LC, other treatments known to influence TH were examined. Reserpine treatment, shown previously to increase levels of TH, was found to increase both LC firing rate and levels of soluble cAMP-dependent protein kinase activity in the LC. 6-Hydroxydopamine, shown previously to increase levels of TH and firing rate of LC neurons, also increased soluble levels of protein kinase activity. Other treatments known to either increase (adrenalectomy) or decrease (chronic imipramine) levels of TH in the LC were also found to increase or decrease, respectively, levels of cAMP-dependent protein kinase activity in this brain region.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coordinate regulation of the cyclic AMP system with firing rate and expression of tyrosine hydroxylase in the rat locus coeruleus: effects of chronic stress and drug treatments. 134 39

In skeletal muscles, calcitonin gene-related peptide (CGRP) released from motor nerve terminals and humoral catecholamines stimulate adenylate cyclase (AC) and enhance muscle contraction. The effects of denervation and treatment with reserpine on twitch contraction and the AC system in rat diaphragm were investigated. The basal levels of twitch contraction and AC activity of the diaphragm of rats were both increased 2 weeks after phrenic nerve denervation but were not altered by treatment with reserpine. Reserpine treatment provoked supersensitivity of AC to isoproterenol, without affecting the response to CGRP. On the other hand, denervation decreased the activation of AC and enhancement of twitch contraction by CGRP, without affecting the responses to isoproterenol. These data suggest that denervation causes up-regulation of AC as a result of loss of CGRP release from nerve terminal and that depletion of catecholamines by reserpine treatment supersensitizes the responses at the beta-adrenoceptor level. Thus, nervous and humoral factors regulate the AC system in striated muscle by different mechanisms.
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PMID:Different natures of supersensitivity of adenylate cyclase stimulated by calcitonin gene-related peptide and isoproterenol in rat diaphragm after denervation and reserpine treatment. 172 42

The effects of the monoamine depleting drugs oxypertine, tetrabenazine and reserpine were compared with those of the dopamine receptor antagonists, chlorpromazine and trifluoperazine, on behavioural and biochemical indices of dopamine function in the brain. Oxypertine (0.625-20 mg/kg, i.p.), chlorpromazine (0.625-20 mg/kg i.p.) and trifluoperazine (0.0625-2.0 mg/kg i.p.), administered to rats 1 hr previously, inhibited stereotyped behaviour induced by both amphetamine (5.0 mg/kg i.p.) and apomorphine (1.0 mg/kg, s.c.) in a dose-dependent manner. Tetrabenazine (0.625-20 mg/kg i.p., 1 hr previously) inhibited stereotypy induced by amphetamine but not that induced by apomorphine. Reserpine (0.1 10 mg/kg i.p., 6 hr previously) did not inhibit, but in larger doses, tended to enhance the stereotyped responses to both amphetamine and apomorphine. Oxypertine (10 mg/kg, i.p., 1 hr previously), tetrabenazine (5 mg/kg i.p., 1 hr previously) and reserpine (2.5 mg/kg i.p., 6 hr previously) reduced the content of dopamine in the striatum but increased the concentrations of homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC). Chlorpromazine (5 mg/kg i.p.) and trifluoperazine (0.5 mg/kg i.p.), given 1 hr previously, did not alter concentrations of dopamine in the striatum but increased those of HVA and DOPAC. Oxypertine, chlorpromazine and trifluoperazine weakly inhibited dopamine-stimulated adenylate cyclase in homogenates of the striatum in the rat. Tetrabenazine and reserpine had no effect. Similarly, trifluoperazine and chlorpromazine displaced the specific binding of [3H]piflutixol to membranes from the striatum. Oxypertine also was weakly effective, but tetrabenazine and reserpine were without effect. Trifluoperazine, chlorpromazine and oxypertine displaced specific binding of [3H]spiperone and [3H]N,n-propylnorapomorphine (NPA) to preparations of the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of the acute actions of amine-depleting drugs and dopamine receptor antagonists on dopamine function in the brain in rats. 288 88

The effects of a reserpine treatment inducing supersensitivity to the cardiac effects of agonists (2.5 mg/kg per day for 2 days) was studied on guinea-pig cardiac adenylate cyclase (AC) activity. Reserpine treatment had no effect on basal or Gpp(NH)p (10(-7) M)-stimulated activities. Histamine (2 X 10(-6) and 10(-4) M) stimulation of guinea-pig AC was not influenced by the reserpine treatment. Epinephrine stimulation of AC was affected by reserpine and was characterized by an upward shift of the epinephrine dose-response curve with no change in the epinephrine EC50. The results indicate that the enhancement of cyclic AMP production is an important factor in the reserpine-induced cardiac supersensitivity to beta-adrenoceptor agonists.
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PMID:Reserpine-induced supersensitivity in adenylate cyclase preparations from guinea-pig heart. 365 43

Rats were treated with lithium, imipramine, reserpine, and lithium combined with imipramine or reserpine. Lithium was given in the diet (40 mmol/kg) resulting in a serum-Li+ level of 0.5-0.6 mmol/l. Other drugs were dissolved in 0.9% saline and given intraperitoneally once or twice daily. After 3 weeks of treatment, forskolin-stimulated adenylate cyclase activity was measured in cerebral cortex homogenates. Reserpine did not affect the forskolin stimulation, while both imipramine and lithium caused a decrease in this activity. The combined treatments lithium-imipramine and lithium-reserpine also exhibited a clear decrease in forskolin stimulation, but the effect of concomitant lithium and imipramine treatment did not differ from the effect seen after any of the treatments alone. The unstimulated activity was unaltered by all treatments. The inhibition of lithium and imipramine on the forskolin stimulation indicates an interference of these two drugs with the forskolin-mediated activation of the adenylate cyclase.
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PMID:Forskolin-stimulated adenylate cyclase activity in rat cerebral cortex following chronic treatment with psychotropic drugs. 654 99

We have developed an assay for serotonin (5-HT) stimulation of adenylate cyclase activity in membranes from adult guinea pig hippocampus. The response to 5-HT is concentration-dependent, with an EC50 of 0.01 microM, a shallow slope, and mean maximal stimulation of 90% over basal activity. The response to 5-HT is GTP-dependent and additive to the maximal stimulation by histamine. Micromolar concentrations of the known 5-HT receptor agonists, tryptamine and 5-methoxytryptamine, also stimulate cAMP production in this system, and their effect is not additive to that elicited by a maximal concentration of 5-HT. These results are consistent with the hypothesis that the response to 5-HT is elicited through a distinct receptor coupled to adenylate cyclase; the magnitude and the reproducibility of the 5-HT response in this system should make it useful for receptor classification. To examine the effect of prior exposure to endogenous 5-HT on the responsiveness of the system, we assayed 5-HT stimulation of enzyme activity in membranes prepared from animals 25-27 hrs after treatment with a single injection of reserpine (5 mg/kg, i.p.). The mean maximal stimulation of adenylate cyclase by 5-HT was increased to 150% over basal activity with no effect on the EC50 or slope of the 5-HT concentration-response curve. Reserpine pretreatment did not affect basal activity or histamine-stimulated adenylate cyclase activity. These results are discussed in the context of a hypothesis that endogenous 5-HT normally exerts a desensitizing effect on its receptors in situ.
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PMID:Enhanced serotonin-stimulated adenylate cyclase activity in membranes from adult guinea pig hippocampus. 657 50