5-HT2 receptor subtypes: A family re-united?

Baxter, G.S.; Kennett, Guy A.; Blackburn, T.P.; Blaney, Frank E.

doi:10.1016/s0165-6147(00)88991-9

Cited by 330 publications

(227 citation statements)

References 23 publications

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“…The effect of these antagonists was dose dependent. Piperidine (2 M) produced a smaller but still significant reduction in the frequency of the fictive respiratory activity (to 88.57 Ϯ 6.13% of control; n ϭ 4; p Ͻ 0.05) Studies in other systems indicate that 5-HT 2A antagonists can also act on the 5-HT 2C receptor (Baxter et al, 1995;Barnes and Sharp, 1999;Jerman et al, 2001). Although the 5-HT 2A -receptor antagonists ketanserine, piperidine, and spiperone have a higher affinity for the 5-HT 2A receptor, it was important to compare their actions with those of a specific 5-HT 2C antagonist (SB206553).…”

Section: Effects Of Pharmacological Activation and Blockade Of 5-ht 2mentioning

confidence: 92%

Endogenous Activation of Serotonin-2A Receptors Is Required for Respiratory Rhythm GenerationIn Vitro

2002

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Endogenous amines and peptides continuously modulate the activity of neuronal networks and are required even for their normal operation. The respiratory rhythm generator, localized in the pre-Bö tzinger complex, is not an exception. This network is modulated by various neurotransmitters, including serotonin (5-HT). In this study, we isolated the respiratory network in brainstem slices and demonstrate that the endogenous activation of 5-HT 2A is required for the generation of the respiratory rhythm in vitro. At the network level, activation of 5-HT 2A receptors with 4-iodo-2,5-dimethoxyamphetamine or the 5-HT uptake blocker alaproclate increased the frequency of respiratory activity. Blockade of endogenously activated 5-HT 2A receptors with three different antagonists decreased the frequency, amplitude, and regularity of respiratory population activity, an effect that was blocked by protein kinase C (PKC) activators. At the cellular level, blockade of 5-HT 2A receptors reduced the action potential discharge in all examined respiratory neurons, which was associated with a reduction in the fast and the persistent sodium current. Continuous application of 5-HT 2A -receptor antagonists differentially affected pacemaker neurons. Pacemaker activity was eliminated in cadmiuminsensitive pacemaker neurons. In cadmium-sensitive pacemaker neurons, the frequency of pacemaker activity was unaffected and the amplitude of pacemaker bursts was enhanced. It is assumed that cadmium-insensitive pacemakers rely on the persistent sodium current, whereas cadmium-sensitive pacemakers depend on the activation of calcium currents. We conclude that endogenously activated 5-HT 2A receptors are required for maintaining fictive respiratory activity in the brainstem slice by modulating sodium conductances via a PKC pathway.

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Section: Effects Of Pharmacological Activation and Blockade Of 5-ht 2mentioning

confidence: 92%

Endogenous Activation of Serotonin-2A Receptors Is Required for Respiratory Rhythm GenerationIn Vitro

2002

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“…Furthermore, 5-HT receptors may have a causative relevance to human mental abnormalities and pathology, including anxiety, psychotic depression, migraine, substance dependency, and schizophrenia (Baxter et al, 1995). In humans and rodents, three subtypes of the 5-HT 2 receptor (5-HT 2 R) gene family (5-HT 2A R, 5-HT 2B R, and 5-HT 2C R) have been identified (Baxter et al, 1995).RNA editing plays a critical role in the expression of certain gene products by changing the sequence context of mRNAs, which results in synthesis of proteins not encoded in the gene sequence (Smith et al, 1997). One type of RNA editing involves the conversion of adenosine residues into inosine in transcripts of genes such as glutamate receptor ion channels (Sommer et al, 1991;Lomeli et al, 1994) and 5-HT 2C Rs (Burns et al, 1997).…”

mentioning

confidence: 99%

Altered G Protein‐Coupling Functions of RNA Editing Isoform and Splicing Variant Serotonin_2C Receptors

Wang

O’Brien

Chen

et al. 2000

Journal of Neurochemistry

191

206

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Different isoforms of serotonin subtype 2C receptor (5-HT 2C R) with altered G protein-coupling efficacy are generated by RNA editing, which converts genomically encoded adenosine residues into inosines. In combination, editing of five sites all located within the second intracellular loop region of 5-HT 2C R mRNA changes the gene-encoded Ile, Asn, and Ile at positions 156, 158, and 160, respectively. We analyzed the G protein-coupling functions of previously unreported editing isoform receptors. An ϳ13-fold reduction in the agonist potency for G protein-coupling stimulation as well as a significantly reduced basal level activity was observed with the thalamus-specific isoform carrying Ile 156 , Gly 158 , and Val 160 (5-HT 2C R-IGV). In contrast, the agonist was four-to fivefold less potent with 5-HT 2C R-MSV and -IDV, detected in the amygdala and choroid plexus, respectively, indicating a dominant role for the amino acid residue at position 158 in receptor functions. We also identified a splicing variant receptor with a truncated C terminus that displayed no ligand binding capacity or G protein-coupling activity. Examination of the alternatively spliced RNA encoding this truncated receptor suggests that editing of this variant RNA occurs after completion of splicing, resulting in complete editing at all five sites. Key Words: Serotonin 5-HT 2C receptor-RNA editing-RNA splicing-Doublestranded RNA adenosine deaminase -Adenosine deaminases that act on RNA-G protein coupling. J. Neurochem. 74, 1290Neurochem. 74, -1300Neurochem. 74, (2000.Members of the serotonin [5-hydroxytryptamine (5-HT)] receptor gene family are believed to play important roles in physiological and behavioral processes such as circadian rhythms and feeding behavior. Furthermore, 5-HT receptors may have a causative relevance to human mental abnormalities and pathology, including anxiety, psychotic depression, migraine, substance dependency, and schizophrenia (Baxter et al., 1995). In humans and rodents, three subtypes of the 5-HT 2 receptor (5-HT 2 R) gene family (5-HT 2A R, 5-HT 2B R, and 5-HT 2C R) have been identified (Baxter et al., 1995).RNA editing plays a critical role in the expression of certain gene products by changing the sequence context of mRNAs, which results in synthesis of proteins not encoded in the gene sequence (Smith et al., 1997). One type of RNA editing involves the conversion of adenosine residues into inosine in transcripts of genes such as glutamate receptor ion channels (Sommer et al., 1991;Lomeli et al., 1994) and 5-HT 2C Rs (Burns et al., 1997). The A-to-I RNA editing mechanism requires the doublestranded RNA (dsRNA) structure formed around the editing sites (Higuchi et al., 1993;Egebjerg et al., 1994;Lomeli et al., 1994;Burns et al., 1997) and adenosine deaminases that act on RNA (ADARs) (Kim et al., 1994;O'Connell et al., 1995;Dabiri et al., 1996; Melcher et al., 1996a,b;Bass et al., 1997;Gerber et al., 1997;Lai et al., 1997). Members of the ADAR gene family share some structural similarities, such as...

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“…Ketanserin also differentiates between the three different subtypes, with pKi values of 8.9, 7.0 and 5.4 corresponding to a selectivity of 5-HT2A>5-HT2C>5-HT2B (Baxter et al, 1995; reviewed by Barnes and Sharp, 1999). This indicates that ketanserin is almost 100-fold more and over 1000-fold more selective for 5-HT2A receptors than for either 5-HT2C or 5-HT2B receptors, respectively.…”

Section: -Ht 2 -Like Receptor Triggers Urea Excretionmentioning

confidence: 95%

“…In mammals, α-methyl-5-HT shows a selectivity between the three different 5-HT2 receptor subtypes, with pEC50 values of 8.4, 7.3 and 6.1 corresponding to a selectivity of 5-HT2B>5-HT2C>5-HT2A (Baxter et al, 1995; reviewed by Barnes and Sharp, 1999). Ketanserin also differentiates between the three different subtypes, with pKi values of 8.9, 7.0 and 5.4 corresponding to a selectivity of 5-HT2A>5-HT2C>5-HT2B (Baxter et al, 1995; reviewed by Barnes and Sharp, 1999).…”

Section: -Ht 2 -Like Receptor Triggers Urea Excretionmentioning

confidence: 99%

Dogmas and controversies in the handling of nitrogenous wastes:5-HT2-like receptors are involved in triggering pulsatile urea excretion in the gulf toadfish,Opsanus beta

McDonald

Walsh

2004

Journal of Experimental Biology

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SUMMARYWhen injected arterially, serotonin (5-hydroxytryptamine; 5-HT) has been shown to elicit naturally sized urea pulse events in the gulf toadfish, Opsanus beta. The goal of the present study was to determine which 5-HT receptor(s) was involved in mediating this serotonergic stimulation of the pulsatile excretion mechanism. Toadfish were surgically implanted with caudal arterial catheters and intraperitoneal catheters and injected with either 8-OH-DPAT (1 μmol kg–1), a selective 5-HT1A receptor agonist, α-methyl-5-HT (1 μmol kg–1), a 5-HT2 receptor agonist, or ketanserin, a 5-HT2 receptor antagonist (0.01, 0.1, 1 and 10 μmol kg–1) plus α-methyl-5-HT. 8-OH-DPAT injection did not mediate an increase in urea excretion, ruling out the involvement of 5-HT1A receptors in pulsatile excretion. However, within 5 min,α-methyl-5-HT injection caused an increase in the excretion of urea in>95% (N=27) of the fish injected, with an average pulse size of 652±102 μmol N kg–1 (N=26). Withα-methyl-5-HT injection there was no corresponding increase in ammonia or [3H]PEG 4000 permeability. Urea pulses elicited byα-methyl-5-HT were inhibited in a dose-dependent fashion by the 5-HT2 receptor antagonist ketanserin, which at low doses caused a significant inhibition of pulse size and at higher doses significantly inhibited the occurrence of pulsatile excretion altogether. However, neither 8-OH-DPAT nor α-methyl 5-HT injection had an effect on plasma cortisol or plasma urea concentrations. These findings suggest the involvement of a 5-HT2-like receptor in the regulation of pulsatile urea excretion.

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5-HT2 receptor subtypes: A family re-united?

Cited by 330 publications

References 23 publications

Endogenous Activation of Serotonin-2A Receptors Is Required for Respiratory Rhythm GenerationIn Vitro

Endogenous Activation of Serotonin-2A Receptors Is Required for Respiratory Rhythm GenerationIn Vitro

Altered G Protein‐Coupling Functions of RNA Editing Isoform and Splicing Variant Serotonin_2C Receptors

Dogmas and controversies in the handling of nitrogenous wastes:5-HT2-like receptors are involved in triggering pulsatile urea excretion in the gulf toadfish,Opsanus beta

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5-HT2 receptor subtypes: A family re-united?

Cited by 330 publications

References 23 publications

Endogenous Activation of Serotonin-2A Receptors Is Required for Respiratory Rhythm GenerationIn Vitro

Endogenous Activation of Serotonin-2A Receptors Is Required for Respiratory Rhythm GenerationIn Vitro

Altered G Protein‐Coupling Functions of RNA Editing Isoform and Splicing Variant Serotonin2C Receptors

Dogmas and controversies in the handling of nitrogenous wastes:5-HT2-like receptors are involved in triggering pulsatile urea excretion in the gulf toadfish,Opsanus beta

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Altered G Protein‐Coupling Functions of RNA Editing Isoform and Splicing Variant Serotonin_2C Receptors