Multiplicity of mechanisms of serotonin receptor signal transduction

Raymond, John R.; Mukhin, Y.; Gelasco, Andrew; Turner, Justin H.; Collinsworth, Georgiann; Gettys, Thomas W.; Grewal, Jasmaninder Singh; Garnovskaya, Maria N.

doi:10.1016/s0163-7258(01)00169-3

Cited by 411 publications

(352 citation statements)

References 351 publications

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“…Increased IP 3 leads to an increase in intracellular calcium while DAG activates PKC. In a variety of cell culture systems, PKC has been shown to lead to desensitization of 5-HT 1A receptors [32,33] and it has been hypothesized that a PKC-mediated mechanism might account for DOI's ability to attenuate the effects of a 5-HT 1A receptor agonist on lordosis behavior [39]. The current findings are consistent with this hypothesis.…”

Section: Discussionsupporting

confidence: 86%

“…For Correspondence: Dr. Lynda Uphouse, Department of Biology, Texas Woman's University, Denton, TX 76204, Phone: (940) 898-2356, FAX: (940) 898-2382, Email: Luphouse@mail.twu.edu5-HT 1A receptors are coupled to Gi/o/z proteins and mediate multiple intracellular responses including inhibition of adenylate cyclase, opening of a K + channel, and inhibition of Ca 2+ channels [32]. Effects of 5-HT 1A receptors on ion channels probably contribute to the decrease in neuronal firing, characteristic of activation of 5-HT 1A receptors [1,19,28].…”

Section: Introductionmentioning

confidence: 99%

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The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior

Selvamani

Lincoln

Uphouse

2007

Behavioural Brain Research

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Ovariectomized rats with bilateral cannulae near the ventromedial nucleus of the hypothalamus were hormonally primed with 10μg estradiol benzoate and 500μg progesterone. Sexually receptive females were infused bilaterally with 200 ng of the 5-HT 1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), or with a combination of 200 ng 8-OH-DPAT and 2000 ng of the 5-HT 2 receptor agonist, (±)-2,5-dimethoxy-4-iodophenyl-2-aminopropane HCl (DOI). 8-OH-DPAT inhibited lordosis behavior and DOI reduced this inhibition. However, if females were preinfused with the PKC inhibitor, bisindolymaleimide I hydrochloride (BIM), DOI's effect was eliminated. BIM's attenuation of the effects of DOI was time-dependent. When BIM was infused 90 min, but not 30 min, before the 5-HT receptor agonists, BIM eliminated DOI's protection against the lordosisinhibiting effects of 8-OH-DPAT. A concentration of BIM as low as 10 −5 nmol in a 0.5μl infusion volume was effective and there was little evidence of dose responsivity between 10 −5 and 10 −1 nmol of BIM. In contrast, prior infusion with vehicle or with 10 −7 nmol BIM had no impact on the female's response to the 5-HT receptor agonists. These findings allow the suggestion that DOI's ability to increase PKC may be responsible for attenuation of the effects of 8-OH-DPAT on lordosis behavior. KeywordsPKC inhibitor; 5-HT 1A receptors; 5-HT 2 receptors; ovariectomized; sexual behavior IntroductionWithin the ventromedial nucleus of the hypothalamus (VMN), serotonin (5-HT) modulates female rat sexual behavior by acting on multiple 5-HT receptors [39]. Lordosis behavior, a supraspinal estrogen-dependent reflex of sexually receptive females [29], is inhibited by 5-HT 1A receptor agonists and facilitated by 5-HT 2 receptor agonists and their coactivation attenuates the lordosis-inhibitory effects of 5-HT 1A receptor agonists [39]. We have proposed that this 5-HT 1A /5-HT 2 receptor interaction enables the female to fine-tune her behavior so that it is most adaptive to environmental conditions [42]. However, the mechanisms for this interaction are not known.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior

Selvamani

Lincoln

Uphouse

2007

Behavioural Brain Research

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“…The 5-HT 1 receptors (5-HT 1A , 5-HT 1B , 5-HT 1D , 5-HT 1E , 5-HT 1F ) are coupled to Ga i /Ga o signaling proteins; the 5-HT 2 receptors (5-HT 2A , 5-HT 2B, 5-HT 2C ) are coupled to Ga q signaling proteins; the 5-HT 4 , 5-HT 6 , and 5-HT 7 receptors are coupled to Gs proteins. The coupling mechanism for the 5-HT 5 receptors (5-HT 5A and 5HT 5B ) remains unknown (Raymond et al, 2001). High densities of 5-HT 1A receptors have been reported in the limbic areas and these receptors are negatively coupled to adenylyl cyclase (AC) via pertussis-toxin-sensitive Ga i and/ or Ga o proteins (De Vivo and Maayani, 1986;Weiss et al, 1986).…”

Section: Bdnfmentioning

confidence: 99%

Interaction between BDNF and Serotonin: Role in Mood Disorders

Martinowich

2007

Neuropsychopharmacol

657

458

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Brain-derived neurotrophic factor (BDNF) and serotonin (5-hydroxytryptamine, 5-HT) are two seemingly distinct signaling systems that play regulatory roles in many neuronal functions including survival, neurogenesis, and synaptic plasticity. A common feature of the two systems is their ability to regulate the development and plasticity of neural circuits involved in mood disorders such as depression and anxiety. BDNF promotes the survival and differentiation of 5-HT neurons. Conversely, administration of antidepressant selective serotonin reuptake inhibitors (SSRIs) enhances BDNF gene expression. There is also evidence for synergism between the two systems in affective behaviors and genetic epitasis between BDNF and the serotonin transporter genes.

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“…However, all 5-HT receptors belong to the G-protein-coupled receptor superfamily, with the exception of the 5-HT 3 receptor, which is a ligand-gated ion channel (Raymond et al, 2001;Hoyer et al, 2002). The possibility that 5-HT 3 receptors are involved in the negative effects of 5-HT on the generation of DA neurons was tested in the present experiments.…”

Section: Discussionmentioning

confidence: 99%

Serotonin decreases generation of dopaminergic neurons from mesencephalic precursors via serotonin type 7 and type 4 receptors

Parga

Rodríguez‐Pallares

Muñoz

et al. 2006

Developmental Neurobiology

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Inductive signals mediating the differentiation of neural precursors into serotonergic (5-HT) or dopaminergic neurons have not been clarified. We have recently shown that in cell aggregates obtained from rat mesencephalic precursors, reduction of serotonin levels induces a marked increase in generation of dopaminergic neurons. In the present study we treated rat neurospheres with antagonists of the main subtypes of 5-HT receptors, 5-HT transport inhibitors, or 5-HT receptor agonists, and studied the effects on generation of dopaminergic neurons. Cultures treated with Methiothepin (5-HT 1,2,5,6,7 receptor antagonist), the 5-HT 4 receptor antagonist GR113808, or the 5-HT 7 receptor antagonist SB 269970 showed a significant increase in generation of dopaminergic cells. Treatment with the 5-HT 1B/1D antagonist GR 127935, the 5-HT 2 antagonist Ritanserin, the 5-HT transporter inhibitor Fluoxetine, the dopamine and norepinephrine transport inhibitor GBR 12935, or with both inhibitors together, or 5-HT 4 or 5-HT 7 receptor agonists induced significant decreases in generation of dopaminergic cells. Cultures treated with WAY100635 (5-HT 1A receptor antagonist), the 5-HT 3 receptor antagonist Ondasetron, or the 5-HT 6 receptor antagonist SB 258585 did not show any significant changes. Therefore, 5-HT 4 and 5-HT 7 receptors are involved in the observed serotonininduced decrease in generation of dopaminergic neurons from proliferating neurospheres of mesencephalic precursors. 5-HT 4 and 5-HT 7 receptors were found in astrocytes and serotonergic cells using double immunolabeling and laser confocal microscopy, and the glial receptors appeared to play a major role. '

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Multiplicity of mechanisms of serotonin receptor signal transduction

Cited by 411 publications

References 351 publications

The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior

The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior

Interaction between BDNF and Serotonin: Role in Mood Disorders

Serotonin decreases generation of dopaminergic neurons from mesencephalic precursors via serotonin type 7 and type 4 receptors

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