Pertussis toxin treatment prevents 5-HT5a receptor-mediated inhibition of cyclic AMP accumulation in rat C6 glioma cells

Thomas, Elizabeth A.; Matli, Jennifer R.; Hu, John L.; Carson, Monica J.; Sutcliffe, J. Gregor

doi:10.1002/1097-4547(20000701)61:1<75::aid-jnr9>3.0.co;2-9

Cited by 22 publications

(15 citation statements)

References 26 publications

(35 reference statements)

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“…When 5-HT 5A receptor-expressing cells were treated with 0.1 lg/mL PTX, 5-HT-induced inhibition was nulled, and reversed to the stimulated level (152 ± 25%, n ¼ 4) seen in the untransfected cells. This result suggests that 5-HT 5A receptors were functionally expressed in C6 glioma cells and coupled to Gi/Go proteins as reported previously (Francken et al 1998;Hurley et al 1998;Thomas et al 2000) (Fig. 2).…”

Section: Resultssupporting

confidence: 89%

“…Cellular cyclic AMP accumulation experiments were performed by a modification of a previously described method (Thomas et al 2000). C6 glioma cells (or human 5-HT 5A -transfected C6 glioma cells) were plated in 96-well culture dishes at a density of 5 · 10 4 cells/well and cultured overnight.…”

Section: Measurement Of Cyclic Amp Amount In C6 Glioma Cellsmentioning

confidence: 99%

“…Mouse, rat and human 5-HT 5A receptors have been expressed in various mammalian cells using transfection. Inhibition of adenylyl cyclase via coupling to pertussis toxin (PTX)-sensitive Gi/Go proteins has been reported (Francken et al 1998;Hurley et al 1998;Thomas et al 2000). Recently, it was reported that the human 5-HT 5A receptors were able to couple to the G-protein-activated inward rectifying potassium (GIRK) channel, when expressed in Xenopus oocytes (Grailhe et al 2001).…”

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Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways

Нода

Yasuda

Okada

et al. 2003

Journal of Neurochemistry

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Human serotonin 5A (5-HT 5A ) receptors were stably expressed in undifferentiated C6 glioma. In 5-HT 5A receptors-expressing cells, accumulation of cAMP by forskolin was inhibited by 5-HT as reported previously. Pertussis toxin-sensitive inhibition of ADP-ribosyl cyclase was also observed, indicating a decrease of cyclic ADP ribose, a potential intracellular second messenger mediating ryanodine-sensitive Ca 2+ mobilization. On the other hand, 5-HT-induced outward currents were observed using the patch-clamp technique in whole-cell configuration. The 5-HT-induced outward current was observed in 84% of the patched 5-HT 5A receptor-expressing cells and was concentration-dependent. The 5-HT-induced current was inhibited when intracellular K + was replaced with Cs + but was not significantly inhibited by typical K + channel blockers. The 5-HT-induced current was significantly attenuated by 1,2-bis(2-aminophenoxy)ethane-N,N,N¢,N¢-tetraacetic acid (BAPTA) in the patch pipette. Depleting intracellular Ca 2+ stores by application of caffeine or thapsigargin also blocked the 5-HT-induced current. Blocking G protein, the inositol triphosphate (IP3) receptor, or pretreatment with pertussis toxin, all inhibited the 5-HT-induced current. IP3 showed a transient increase after application of 5-HT in 5-HT 5A receptor-expressing cells. It was concluded that in addition to the inhibition of cAMP accumulation and ADP-ribosyl cyclase activity, 5-HT 5A receptors regulate intracellular Ca 2+ mobilization which is probably a result of the IP3-sensitive Ca 2+ store. These multiple signal transduction systems may induce complex changes in the serotonergic system in brain function. Keywords: adenylyl cyclase, ADP ribosyl cyclase, cAMP, IP3, 5-HT 5A receptors, patch-clamp. The neurotransmitter serotonin (5-HT) is involved in the control of diverse physiological processes including sleep, sexual behavior, food intake, locomotion and mood. At least 13 different 5-HT receptors have been identified to date. The present work concerns one of these, the 5-HT 5 receptor, which belongs to the superfamily of G protein-coupled metabotropic receptors.The two members of the 5-HT 5 receptor subfamily, 5-HT 5A and 5-HT 5B , were identified in mice (Plassat et al. 1992;Matthes et al. 1993) and subsequently in rats (Erlander et al. 1993;Wisden et al. 1993). A cDNA encoding the 5-HT 5A receptor has been cloned from human tissues, while the 5-HT 5B receptor does not seem to be functionally expressed

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Section: Resultssupporting

confidence: 89%

Section: Measurement Of Cyclic Amp Amount In C6 Glioma Cellsmentioning

confidence: 99%

mentioning

confidence: 99%

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Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways

Нода

Yasuda

Okada

et al. 2003

Journal of Neurochemistry

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“…Drugs: (i) The universal 5-HT receptor agonist, 5-hydroxytryptamine hydrochloride, acting potently at 5-HT 2A and 5-HT 2B receptors (Doyle et al, 1986; Misane and Ogren, 2000; Li et al, 2010), as well as at 5-HT 6 and 5-HT 7 receptors but less potently at 5-HT 1 receptors (Granados-Soto et al, 2010); 5-HT 3 (Chetty et al, 2006), 5-HT 4 (Prins et al, 2000), 5-HT 5 (Thomas et al, 2000; Nelson, 2004), and 5-HT 6 (Monsma et al, 1993) receptors; (ii) fluoxetine hydrochloride and paroxetine hydrochloride (from Sigma-Aldrich, St. Louis, MO, USA), subtype-specific, almost equipotent agonists at the astrocytic 5-HT 2B receptor; (iii) methiothepin maleate (1-[10,11-dihydro-8-(methyl-thio)dibenzo( Z )[ b,f ]thiepin-10-yl]-4-methylpiperazine maleate), from Research Biochemicals, Inc, a non-specific antagonist of all 5-HT receptors, except 5-HT 3 and 5-HT 4 (Misane and Ogren, 2000), which has high affinity for 5-HT 2A (Briejer et al, 1997) and 5-HT 2B receptors (Glusa and Pertz, 2000), 5-HT 5 receptors (Thomas et al, 2000), 5-HT 6 receptors (Misane and Ogren, 2000) and 5-HT 7 receptors (Jänichen et al, 2005), but lower affinity for at least some of the 5-HT 1 receptors (Misane and Ogren, 2000); (iv) the selective 5-HT 2B/C receptor antagonist SB221284 (2,3-dihydro-5-(methylthio)- N -3-pyridinyl-6-(trifluoromethyl)-1 H -indole-1-carboxamide), from Tocris Cookson Ltd. UK. All drugs were prepared in sterile physiological saline (154 mM NaCl).…”

Section: Methodsmentioning

confidence: 99%

Serotonin mediation of early memory formation via 5-HT2B receptor-induced glycogenolysis in the day-old chick

Gibbs

Hertz

2014

Front. Pharmacol.

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Investigation of the effects of serotonin on memory formation in the chick revealed an action on at least two 5-HT receptors. Serotonin injected intracerebrally produced a biphasic effect on memory consolidation with enhancement at low doses and inhibition at higher doses. The non-selective 5-HT receptor antagonist methiothepin and the selective 5-HT2B/C receptor antagonist SB221284 both inhibited memory, suggesting actions of serotonin on at least two different receptor subtypes. The 5-HT2B/C and astrocyte-specific 5-HT receptor agonist, fluoxetine and paroxetine, enhanced memory and the effect was attributed to glycogenolysis. Inhibition of glycogenolysis with a low dose of DAB (1,4-dideoxy-1,4-imino-D-arabinitol) prevented both serotonin and fluoxetine from enhancing memory during short-term memory but not during intermediate memory. The role of serotonin on the 5-HT2B/C receptor appears to involve glycogen breakdown in astrocytes during short-term memory, whereas other published evidence attributes the second period of glycogenolysis to noradrenaline.

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“…The 5-HT5A receptor is a metabotropic receptor mostly coupled to G i/o protein in different cell systems (Thomas, 2006;Thomas et al, 2000), but the coupling mechanism in native tissues is not clearly established (Thomas, 2006;Dutton et al, 2008). For further elucidation of the role of the 5-HT5A receptor, a receptor knockout mouse strain was established.…”

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confidence: 99%

Effect of 5-HT5A antagonists in animal models of schizophrenia, anxiety and depression

Kassai

Schlumberger

Kedves

et al. 2012

Behavioural Pharmacology

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The few available data on the pharmacological effect of 5-HT5A receptors suggest that antagonists may have anxiolytic, antidepressant and antipsychotic activity. The aim of our study was to verify these suggestions in relevant animal models. Two 5-HT5A antagonist ligands, SB-699551-A (N-[2-(dimethylamino)ethyl]-N-[[4'-[[(2-phenylethyl)amino]methyl][1,1'-biphenyl]-4-yl]methyl]cyclopentanepropanamide dihydrochloride) (3-60 mg/kg, intraperitoneally) and A-843277 (N-(2,6-dimethoxybenzyl)-N'[4-(4-fluorophenyl)thiazol-2-yl]guanidine) (3-30 mg/kg, intraperitoneally), were examined in the open-field test, in a foot-shock-induced ultrasonic vocalization test, in the forced swim test (FST) and in the amphetamine-induced and phencyclidine-induced hyperlocomotion tests to examine their effect on general behavioural patterns, and their anxiolytic-like, antidepressant-like and antipsychotic-like properties, respectively. In the open-field test, SB-699551-A induced sedation and A-843277 induced writhing. In the ultrasonic vocalization test, SB-699551-A reduced vocalizations, whereas A-843277 was ineffective. In the FST, SB-699551-A was ineffective and A-843277 reduced immobility, but only at the highest dose. In the amphetamine-induced and phencyclidine-induced hyperlocomotion test, both compounds were ineffective. SB-699551-A showed an anxiolytic-like property in the ultrasonic vocalization test; however, this compound has a sedative effect. A-843277 showed an antidepressant-like property in the FST, but its immobility-reducing effect may also be a consequence of abdominal irritation. Consequently, further investigations are required to define the therapeutic potential of 5-HT5A receptor ligands in anxiety, depression and schizophrenia models.

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Pertussis toxin treatment prevents 5-HT5a receptor-mediated inhibition of cyclic AMP accumulation in rat C6 glioma cells

Cited by 22 publications

References 26 publications

Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways

Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways

Serotonin mediation of early memory formation via 5-HT2B receptor-induced glycogenolysis in the day-old chick

Effect of 5-HT5A antagonists in animal models of schizophrenia, anxiety and depression

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