Functional characterization of a novel serotonin receptor (5‐HT<sub>ap2</sub>) expressed in the CNS of <i>Aplysia californica</i>

Barbas, Demian; Zappulla, Jacques; Angers, Stéphane; Bouvier, Michel; Castellucci, Vincent F.; DesGroseillers, Luc

doi:10.1046/j.0022-3042.2001.00703.x

Cited by 49 publications

(50 citation statements)

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“…Stimulation of the 5-HT ap2 receptor by 5-HT in HEK 293 cells inhibits forskolin-induced cAMP accumulation in a dose-dependent manner (Barbas et al 2002). The same result was obtained with the agonist 5-CT.…”

Section: The 5-ht Ap2 Receptor Is Negatively Coupled To Adenylyl Cyclsupporting

confidence: 71%

“…5-HT ap2 mRNA could be detected in the abdominal ganglion (without the bag cells), in the bag cells, and also weakly in the cerebral and pleural-pedal ganglia (Barbas et al 2002). The finding that its expression is restricted to the CNS suggests a potential role for the 5-HT ap2 receptor in modulating synaptic transmission and neuronal excitability.…”

Section: The 5-ht Ap2 Receptor Is Negatively Coupled To Adenylyl Cyclmentioning

confidence: 68%

“…It was demonstrated that phosphorylation by PKA of some GPCRs switches the coupling of the ␤ 2 adrenoreceptor from Gs to Gi (Daaka et al 1997;Zamah et al 2002). Barbas et al (2002) showed that treatment with pertussis toxin not only inhibits a Gi-dependent decrease of cAMP level by the 5-HT ap2 receptor, but also seems to reveal a functional coupling between 5-HT ap2 and Gs-protein that produces an increase in the cAMP level. These findings indicate that stimulation of 5-HT ap2 can modulate overlapping but distinct sets of signal transduction mechanisms, and can give rise to distinct (or even opposing) physiological functions in Aplysia neurons by its dual coupling properties.…”

Section: Cross-talk Between 5-ht Receptors In Aplysiamentioning

confidence: 99%

“…3 H]LSD in a saturable and dose-dependent manner with an estimated K d of 4.37 nM (Barbas et al 2002). The rank order of affinity of various serotonergic agonist and antagonists is given in Table 1.…”

Section: The 5-ht Ap2 Receptor Is Negatively Coupled To Adenylyl Cyclmentioning

confidence: 99%

“…AF372526; Barbas et al 2002). The cDNA contains an open reading frame encoding a protein of 567 aa with a predicted molecular mass of 63 kD.…”

Section: Cloning Of 5-ht Receptors In Aplysiamentioning

confidence: 99%

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Multiple Serotonergic Mechanisms Contributing to Sensitization in Aplysia: Evidence of Diverse Serotonin Receptor Subtypes

Barbas¹,

DesGroseillers²,

Castellucci³

et al. 2003

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105

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The neurotransmitter serotonin (5-HT) plays an important role in memory encoding in Aplysia. Early evidence showed that during sensitization, 5-HT activates a cyclic AMP-protein kinase A (cAMP-PKA)-dependent pathway within specific sensory neurons (SNs), which increases their excitability and facilitates synaptic transmission onto their follower motor neurons (MNs). However, recent data suggest that serotonergic modulation during sensitization is more complex and diverse. The neuronal circuits mediating defensive reflexes contain a number of interneurons that respond to 5-HT in ways opposite to those of the SNs, showing a decrease in excitability and/or synaptic depression. Moreover, in addition to acting through a cAMP-PKA pathway within SNs, 5-HT is also capable of activating a variety of other protein kinases such as protein kinase C, extracellular signal-regulated kinases, and tyrosine kinases. This diversity of 5-HT responses during sensitization suggests the presence of multiple 5-HT receptor subtypes within the Aplysia central nervous system. Four 5-HT receptors have been cloned and characterized to date. Although several others probably remain to be characterized in molecular terms, especially the Gs-coupled 5-HT receptor capable of activating cAMP-PKA pathways, the multiplicity of serotonergic mechanisms recruited into action during learning in Aplysia can now be addressed from a molecular point of view.The marine mollusk Aplysia has proven to be a powerful model system for the study of learning and memory. This animal displays several simple forms of nonassociative learning, such as habituation, dishabituation, and sensitization (Pinsker et al. 1970(Pinsker et al. , 1973Carew et al. 1971), but also more complex forms of associative learning such as classical, operant, and fear conditioning (Carew et al. , 1983Walters et al. 1981; Lechner et al. 2000a,b;Brembs et al. 2002). The strength of this model system arises from the relative simplicity of its central nervous system (CNS), which contains a small number of neurons, some of which are well characterized both morphologically and electrophysiologically. Thus, one can study a specific synaptic connection in different animals subjected to a wide variety of behavioral training protocols. For this reason, it has been possible to discover many of the mechanisms of learning and memory in this animal at the behavioral, cellular, and molecular levels, and provide direct evidence that certain forms of learning rely on the plasticity of individual synaptic connections (for review, see Kandel 2001).One of the best characterized forms of learning in Aplysia is sensitization, in which a noxious stimulus facilitates an animal's pre-existing response to the presentation of another innocuous stimulus. It has been most thoroughly studied in the defensive reflex responses of Aplysia. For example, a mild tactile stimulus applied to the tail evokes the retraction of respiratory organs (gill and siphon) inside the mantle cavity situated on the back of the animal. The stre...

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Section: The 5-ht Ap2 Receptor Is Negatively Coupled To Adenylyl Cyclsupporting

confidence: 71%

Section: The 5-ht Ap2 Receptor Is Negatively Coupled To Adenylyl Cyclmentioning

confidence: 68%

Section: Cross-talk Between 5-ht Receptors In Aplysiamentioning

confidence: 99%

Section: The 5-ht Ap2 Receptor Is Negatively Coupled To Adenylyl Cyclmentioning

confidence: 99%

“…AF372526; Barbas et al 2002). The cDNA contains an open reading frame encoding a protein of 567 aa with a predicted molecular mass of 63 kD.…”

Section: Cloning Of 5-ht Receptors In Aplysiamentioning

confidence: 99%

See 3 more Smart Citations

Multiple Serotonergic Mechanisms Contributing to Sensitization in Aplysia: Evidence of Diverse Serotonin Receptor Subtypes

Barbas¹,

DesGroseillers²,

Castellucci³

et al. 2003

Learn. Mem.

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105

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Isolation, cloning, and tissue expression of a putative octopamine/tyramine receptor from locust visceral muscle tissues

Molaei

Paluzzi

Bendena

et al. 2005

Arch Insect Biochem Physiol

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Octopamine has been shown to play major roles in invertebrate nervous systems as a neurotransmitter, neuromodulator, and neurohormone. Tyramine is the biochemical precursor of octopamine and its neuromodulatory role is now being investigated and clarified in invertebrates, particularly in insects. Both octopamine and tyramine mediate their actions via G protein-coupled receptors (GPCRs) and are believed to play important functions in the regulation of physiological processes in locust oviduct. Here we report the isolation, cloning, and tissue expression of a putative octopamine/tyramine receptor from the locust, Locusta migratoria. Degenerate oligonucleotides in PCR reactions were first used to obtain partial cDNA sequences and then these partial sequences were used in screens to obtain a full-length cDNA. The cloned cDNA is about 3.1 kb long and encodes a protein of 484 amino acid residues with typical characteristics of GPCRs including seven transmembrane domains and many signature residues. The amino acid sequence of the cloned cDNA displays sequence similarities with known GPCRs, particularly octopamine/tyramine receptors. Screening of the locust genomic DNA library resulted in isolation of a genomic DNA with the same size as the cDNA, indicating that the gene is intron-less. RT-PCR and Northern blot analyses revealed the expression of the receptor mRNA in brain, ventral nerve cord, oviduct, and midgut tissues. Southern blot analyses using EcoRI and HindIII restriction endonucleases recognized at least two distinct gene bands.

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Presalvage prostate‐specific antigen (PSA) and PSA doubling time as predictors of biochemical failure of salvage cryotherapy in patients with locally recurrent prostate cancer after radiotherapy

Spiess

Lee

Leibovici

et al. 2006

Cancer

1,924

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BACKGROUND.The value of presalvage cryotherapy serum PSA level in predicting biochemical failure in patients with local recurrence of prostate cancer (PCa) after radiotherapy was documented; however, little is known about the predictive value of prostate‐specific antigen (PSA) doubling time (DT) in this patient group. The purpose of the current study was to evaluate serum PSA level and PSA DT as predictors of salvage cryotherapy outcomes in patients being treated for postradiotherapy locally recurrent PCa.METHODS.The charts of patients treated with salvage cryotherapy were retrospectively reviewed for locally recurrent PCa at the M. D. Anderson Cancer Center from January 1980 to July 2004. Patients who received neoadjuvant or adjuvant hormone therapy were excluded. We assessed pre‐ and postradiotherapy clinical data, pre‐ and postsalvage cryotherapy clinical data, and other variables. Kaplan–Meier and log rank tests were performed to assess unadjusted survival probabilities and 2‐group survival comparisons, respectively. Cox proportional hazards regression models were used to assess the effect of patient characteristics in predicting overall, disease‐specific, and biochemical failure‐free survival.RESULTS.Forty‐nine patients met the eligibility criteria. The median age of patients at diagnosis was 66 years (58–81 years) with the initial clinical stage before radiotherapy most commonly T2 (n = 25) or T3 (n = 21). The median presalvage cryotherapy serum PSA level was 5.9 ng/mL (0.4–23.1 ng/mL) and the presalvage prostatic biopsies were frequently high grade (Gleason grade ≥8 in 51% of patients). The median postsalvage cryotherapy serum PSA level was 0.1 ng/mL (0.1‐9.5 ng/mL), and biochemical failure (defined as a serum PSA level ≥2 ng/mL above the postsalvage cryotherapy PSA nadir) occurred in 26 patients. In these 26 patients, there was a statistically significant difference between pre‐ and postsalvage cryotherapy PSA DTs (12.3 months to 5.6 months, respectively; P = .02). A presalvage cryotherapy serum PSA level >10 ng/mL (P = .002) and PSA DT ≤16 months (P = .06) were found to predict the subsequent risk of biochemical failure.CONCLUSIONS.Presalvage PSA and PSA DT can predict biochemical failure of salvage cryotherapy, although the predictive value of PSA DT only trended toward significance. The statistically significant difference in pre‐ and postsalvage cryotherapy PSA DTs was reflective of aggressive tumor biology. Cancer 2006. © 2006 American Cancer Society.

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Functional characterization of a novel serotonin receptor (5‐HT_ap2) expressed in the CNS of Aplysia californica

Cited by 49 publications

References 50 publications

Multiple Serotonergic Mechanisms Contributing to Sensitization in Aplysia: Evidence of Diverse Serotonin Receptor Subtypes

Multiple Serotonergic Mechanisms Contributing to Sensitization in Aplysia: Evidence of Diverse Serotonin Receptor Subtypes

Isolation, cloning, and tissue expression of a putative octopamine/tyramine receptor from locust visceral muscle tissues

Presalvage prostate‐specific antigen (PSA) and PSA doubling time as predictors of biochemical failure of salvage cryotherapy in patients with locally recurrent prostate cancer after radiotherapy

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Functional characterization of a novel serotonin receptor (5‐HTap2) expressed in the CNS of Aplysia californica

Cited by 49 publications

References 50 publications

Multiple Serotonergic Mechanisms Contributing to Sensitization in Aplysia: Evidence of Diverse Serotonin Receptor Subtypes

Multiple Serotonergic Mechanisms Contributing to Sensitization in Aplysia: Evidence of Diverse Serotonin Receptor Subtypes

Isolation, cloning, and tissue expression of a putative octopamine/tyramine receptor from locust visceral muscle tissues

Presalvage prostate‐specific antigen (PSA) and PSA doubling time as predictors of biochemical failure of salvage cryotherapy in patients with locally recurrent prostate cancer after radiotherapy

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Functional characterization of a novel serotonin receptor (5‐HT_ap2) expressed in the CNS of Aplysia californica