Serotonin elevates intracellular Ca2+ in rat choroid plexus epithelial cells by acting on 5-HT2C receptors

Watson, J.A.; Elliott, A.; Brown, Petra

doi:10.1016/0143-4160(95)90081-0

Cited by 23 publications

(19 citation statements)

References 26 publications

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“…52,53 Conversely, serotonin acts at 5-HT 2c receptors to increase intracellular calcium activity in choroid plexus epithelial cells, both by liberating Ca 2 + from intracellular stores and by activating a Ca 2 + influx pathway. 54 In rat motorneurones serotonin inhibits N and P type calcium currents. 55 In the pathophysiology of migraine, cortical spreading depression may initiate migraine attacks.…”

Section: Role Of Calcium Channels In the Pathophysiology Of Migrainementioning

confidence: 99%

Migraine, ataxia and epilepsy: a challenging spectrum of genetically determined calcium channelopathies

Terwindt

Ophoff²,

Haan

et al. 1998

Eur J Hum Genet

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Clinical and genetic heterogeneity as well as influence of environmental factors have hampered identification of the genetic factors which are involved in episodic diseases such as migraine, episodic ataxia and epilepsy. The study of rare, but clearly genetically determined subtypes, may help to unravel the pathogenesis of the more common forms. Recently, different types of mutation in the brain-specific P/Q type calcium channel α 1A subunit gene (CACNA1A) on chromosome 19p13 were shown to be involved in three human disorders: familial hemiplegic migraine (FHM), episodic ataxia type 2 (EA2), and chronic spinocerebellar ataxia type 6 (SCA6). In addition, evidence is accumulating that the same gene is also involved in the common forms of migraine with and without aura. In the tottering and leaner mouse, which are characterised by epilepsy and ataxia, similar mutations were identified in the mouse homologue of the calcium channel α 1A subunit gene. These findings add to the growing list of episodic (and now also chronic) neurological disorders, which are caused by inherited abnormalities of voltage-dependent ion channels. The findings in migraine illustrate that rare, but monogenic variants of a disorder, may be successfully used to identify candidate genes for the more common, but genetically more complex, forms.

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Section: Role Of Calcium Channels In the Pathophysiology Of Migrainementioning

confidence: 99%

Migraine, ataxia and epilepsy: a challenging spectrum of genetically determined calcium channelopathies

Terwindt

Ophoff²,

Haan

et al. 1998

Eur J Hum Genet

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“…However, differences in the shape of calcium peak induced by serotonin are evidenced between epithelial cells of choroid plexus and the present RCP cells. Addition of serotonin to native rat choroid plexus induced a [Ca 2ϩ ] i peak which was followed by a plateau, whereas in the RCP cells it returned to the baseline value within 100 s (26). This suggests that RCP cells may originate from nonepithelial cells of the choroid plexus.…”

Section: Calcium Signallingmentioning

confidence: 66%

Vasopressin V1a Receptor Signaling in a Rat Choroid Plexus Cell Line

Battle¹,

Preisser

Marteau³

et al. 2000

Biochemical and Biophysical Research Communications

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“…phorylation (7). Although subsequent responses to agonist application are attenuated (desensitized) relative to the first response (7,(17)(18)(19), it is not known whether phosphorylation of the 5-HT 2C receptor plays a role in desensitization. Therefore, we created 5-HT 2C receptor phosphorylation-deficient mutants and examined serotonin responses in phosphoinositide hydrolysis and calcium release experiments.…”

Section: Characterization Of 5-ht 2cmentioning

confidence: 99%

“…In the case of phospholipase C-linked receptors, phosphorylation has been demonstrated to promote desensitization based on observations that receptors lacking the corresponding phosphorylation sites display sustained phosphoinositide hydrolysis responses relative to wild-type receptors (8 -13). Furthermore, a second application of agonist produces amplified phosphoinositide hydrolysis (14) and calcium release (13, 15, 16) by phosphorylation-deficient mutants relative to wild-type receptors, illustrating that mutation of phosphorylation sites involved in desensitization enhances both initial and secondary responses.Although desensitization of 5-HT 2C receptor-mediated responses has been observed in assays that examine phosphoinositide hydrolysis (7, 17), release of intracellular calcium (18,19), and Ca 2ϩ -activated currents (20), it is unknown whether phosphorylation of the 5-HT 2C receptor is involved in desensitization. To address this issue, we identified a 5-HT 2C receptor domain that is required for receptor phosphorylation and performed functional assays with phosphorylation-deficient receptor mutants.…”

mentioning

confidence: 99%

“…Although desensitization of 5-HT 2C receptor-mediated responses has been observed in assays that examine phosphoinositide hydrolysis (7, 17), release of intracellular calcium (18,19), and Ca 2ϩ -activated currents (20), it is unknown whether phosphorylation of the 5-HT 2C receptor is involved in desensitization. To address this issue, we identified a 5-HT 2C receptor domain that is required for receptor phosphorylation and performed functional assays with phosphorylation-deficient receptor mutants.…”

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confidence: 99%

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Deletion of the Serotonin 5-HT2C Receptor PDZ Recognition Motif Prevents Receptor Phosphorylation and Delays Resensitization of Receptor Responses

Backstrom

Price

Reasoner

et al. 2000

Journal of Biological Chemistry

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Phosphorylation-deficient serotonin 5-HT 2C receptors were generated to determine whether phosphorylation promotes desensitization of receptor responses. Phosphorylation of mutant 5-HT 2C receptors that lack the carboxyl-terminal PDZ recognition motif (Ser 458 -SerVal-COOH; ⌬PDZ) was not detectable based on a bandshift phosphorylation assay and incorporation of 32 Serotonin 5-HT 2C (formerly 5-HT 1C ) receptors exists as several isoforms throughout the brain, due to RNA editing and alternative splicing, and function to stimulate phospholipase C through activation of the G protein G q (1). Whereas RNA editing generates isoforms in the second intracellular loop that modify receptor signaling (2-4), alternative splicing creates truncated nonfunctional receptors (5, 6). In addition, agonists promote phosphorylation of nonedited 5-HT 2C receptors (7), raising the possibility that 5-HT 2C receptors are also regulated dynamically.Phosphorylation of G protein-coupled receptors regulates signaling through multiple mechanisms including receptor desensitization, which attenuates second messenger responses. In the case of phospholipase C-linked receptors, phosphorylation has been demonstrated to promote desensitization based on observations that receptors lacking the corresponding phosphorylation sites display sustained phosphoinositide hydrolysis responses relative to wild-type receptors (8 -13). Furthermore, a second application of agonist produces amplified phosphoinositide hydrolysis (14) and calcium release (13, 15, 16) by phosphorylation-deficient mutants relative to wild-type receptors, illustrating that mutation of phosphorylation sites involved in desensitization enhances both initial and secondary responses.Although desensitization of 5-HT 2C receptor-mediated responses has been observed in assays that examine phosphoinositide hydrolysis (7, 17), release of intracellular calcium (18,19), and Ca 2ϩ -activated currents (20), it is unknown whether phosphorylation of the 5-HT 2C receptor is involved in desensitization. To address this issue, we identified a 5-HT 2C receptor domain that is required for receptor phosphorylation and performed functional assays with phosphorylation-deficient receptor mutants. First, we determined that phosphorylation of the 5-HT 2C receptor requires the carboxyl-terminal PDZ (PSD-95 discs-large ZO-1) recognition motif, a domain present in nonedited and edited isoforms of the 5-HT 2C receptor. Next, we found that phosphorylation-deficient receptors display identical initial responses as the wild-type 5-HT 2C receptor in phosphoinositide hydrolysis and calcium release assays. However, phosphorylation-deficient receptors exhibit diminished secondary responses and a delayed recovery relative to wild-type 5-HT 2C receptors. Cells stably expressing 5-HT 2C receptors with a single serine-to-alanine mutation also display decreased receptor phosphorylation and diminished secondary calcium responses. We therefore propose that 5-HT 2C receptor phosphorylation promotes resensitization of 5-HT 2C re...

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Serotonin elevates intracellular Ca2+ in rat choroid plexus epithelial cells by acting on 5-HT2C receptors

Cited by 23 publications

References 26 publications

Migraine, ataxia and epilepsy: a challenging spectrum of genetically determined calcium channelopathies

Migraine, ataxia and epilepsy: a challenging spectrum of genetically determined calcium channelopathies

Vasopressin V1a Receptor Signaling in a Rat Choroid Plexus Cell Line

Deletion of the Serotonin 5-HT2C Receptor PDZ Recognition Motif Prevents Receptor Phosphorylation and Delays Resensitization of Receptor Responses

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