Serotonin sensitive adenylate cyclase in horse brain synaptosomal membranes

Fillion, G.; Rousselle, Jean Claude; Beaudoin, Dominique; Pradelles, Philippe; Goiny, Michel; Dray, F.; Jacob, J.

doi:10.1016/0024-3205(79)90072-9

Cited by 40 publications

(19 citation statements)

References 10 publications

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“…In this latter study the classical serotonin antagonists methysergide and cyproheptadine were used to block the inhibitory effects of serotonin and raphe stimulation, but the specific receptors involved in this response cannot be assessed because of the high concentrations of antagonist used (30-50 mM). Although still controversial, one mechanism of action of serotonin at the 5-HT I site may be via stimulation of adenylate cyclase activity (Fillion et at., 1979;Shenker et at., 1985). In hippocampal membranes, serotonin-stimulated adeny-…”

Section: Serotoninergic Projections To Layer Imentioning

confidence: 99%

The Role of Layer I in Cortical Function

Vogt

1991

Normal and Altered States of Function

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Section: Serotoninergic Projections To Layer Imentioning

confidence: 99%

The Role of Layer I in Cortical Function

Vogt

1991

Normal and Altered States of Function

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“…They are also clearly distinct from those binding 3H-spiroperidol described as 5-HT2 receptors by Peroutka et al [9].…”

Section: Introductionmentioning

confidence: 51%

“…The cerebral receptor for 5-HT appears to be constituted of a recognition site binding 3H-5-HT and an adenylate cyclase which cat alyses the production of cAMP from ATP [6,9]. It has been shown that these sites are neur onal and postsynaptically located [8].…”

Section: Discussionmentioning

confidence: 99%

Postnatal Development of High Affinity Neuronal Recognition Sites for <sup>3</sup>H-5-HT in Rat Brain

Fillion¹,

Hernández²,

Bauguen³

et al. 1982

Dev Neurosci

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The postnatal development of ³H-5-HT specific binding sites has been studied in rat brain. Experimental conditions allowed the characterization of the class of sites corresponding to the synaptosomal receptor for 5-HT. The related affinity constant and maximal binding were measured at various ages after birth. During the second week after birth, the serotonin receptor system developed explosively, the maximal number of sites increasing from a nonsignificant value to that observed in adult rats. Lesion of the presynaptic neurons using 5,6-DHT led to a significant increase of the number of sites.

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“…The ability of ligands to bind to a serotonin receptor was determined by measuring the cyclic AMP (cAMP) induced by serotonin in synaptosomal membrane-enriched fractions (9). Briefly, samples extracted from the rat frontal cortex were incubated for 2 min at room temperature in 50 mM Tris-HCl buffer (pH 7.4) containing 0.5 mM EDTA, 0.4 mM ATP, 2.0 mM MgSO 4 , and 1.0 mM isobutyl methylxanthine.…”

Section: Serotonin Receptor Ligandsmentioning

confidence: 99%

5HT1A Serotonin Receptor Agonists InhibitPlasmodium falciparumby Blocking a MembraneChannel

Locher

Ruben²,

Gut

et al. 2003

Antimicrob Agents Chemother

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To identify new leads for the treatment of Plasmodium falciparum malaria, we screened a panel of serotonin (5-hydroxytryptamine [5HT]) receptor agonists and antagonists and determined their effects on parasite growth. The 5HT1A receptor agonists 8-hydroxy-N-(di-n-propyl)-aminotetralin (8-OH-DPAT), 2,5-dimethoxy-4-iodoamphetamine, and 2,5-dimethoxy-4-bromophenylethylamine inhibited the growth of P. falciparum in vitro (50% inhibitory concentrations, 0.4, 0.7, and 1.5 M, respectively). In further characterizing the antiparasitic effects of 8-OH-DPAT, we found that this serotonin receptor agonist did not affect the growth of Leishmania infantum, Trypanosoma cruzi, Trypanosoma brucei brucei, or Trichostrongylus colubriformis in vitro and did not demonstrate cytotoxicity against the human lung fibroblast cell line MRC-5. 8-OH-DPAT had similar levels of growth inhibition against several different P. falciparum isolates having distinct chemotherapeutic resistance phenotypes, and its antimalarial effect was additive when it was used in combination with chloroquine against a chloroquine-resistant isolate. In a patch clamp assay, 8-OH-DPAT blocked a P. falciparum surface membrane channel, suggesting that serotonin receptor agonists are a novel class of antimalarials that target a nutrient transport pathway. Since there may be neurological involvement with the use of 8-OH-DPAT and other serotonin receptor agonists in the treatment of falciparum malaria, new lead compounds derived from 8-OH-DPAT will need to be modified to prevent potential neurological side effects. Nevertheless, these results suggest that 8-OH-DPAT is a new lead compound with which to derive novel antimalarial agents and is a useful tool with which to characterize P. falciparum membrane channels.Discovery of drugs for the treatment of malaria is essential because of the widespread resistance of Plasmodium falciparum to chloroquine and other drugs. Drug resistance contributes importantly to the 1 to 2 million deaths caused by malaria every year (25, 37). Natural products from traditional medicinal plants have formed the basis of new synthetic antimalarial analogues with potent activity, and numerous other lead compounds have been identified, including alkaloids, quinones, terpenes, and flavonoids (17,26). During the screening of plant extracts used in traditional Polynesian medicine and other natural products for antiviral and antimicrobial activity (19), we found that some serotonin (5-hydroxytryptamine [5HT]) receptor agonists have antimalarial properties. The activity of these agonists was accompanied by the blocking of a membrane channel on parasitized erythrocytes. Serotonin agonists may therefore be useful for the characterization of the membrane transport properties of the malaria parasite and may provide new lead candidates for the treatment of malaria. MATERIALS AND METHODSGrowth inhibition assays. The P. falciparum isolates used were Uganda-Palo Alto (FUP; mefloquine resistant) (10), Falciparum Vietnam Oak Knoll (FVO; chloroquine resistant) (29),...

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Serotonin sensitive adenylate cyclase in horse brain synaptosomal membranes

Cited by 40 publications

References 10 publications

The Role of Layer I in Cortical Function

The Role of Layer I in Cortical Function

Postnatal Development of High Affinity Neuronal Recognition Sites for <sup>3</sup>H-5-HT in Rat Brain

5HT1A Serotonin Receptor Agonists InhibitPlasmodium falciparumby Blocking a MembraneChannel

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