Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are effective drugs for the treatment of several neuropsychiatric disorders associated with reduced serotonergic function. Serotonergic neurons play an important role in the regulation of neuroendocrine function. This review will discuss the acute and chronic effects of SSRIs on neuroendocrine function. Acute administration of SSRIs increases the secretion of several hormones, but chronic treatment with SSRIs does not alter basal blood levels of hormones. However, adaptive changes are induced by long-term treatment with SSRIs in serotonergic, noradrenergic and peptidergic neural function. These adaptive changes, particularly in the function of specific post-synaptic receptor systems, can be examined from altered adrenocorticotrophic hormone (ACTH), cortisol, oxytocin, vasopressin, prolactin, growth hormone (GH) and renin responses to challenges with specific agonists. Neuroendocrine challenge tests both in experimental animals and in humans indicate that chronic SSRIs produce an increase in serotonergic terminal function, accompanied by desensitization of post-synaptic 5-HT1A receptor-mediated ACTH, cortisol, GH and oxytocin responses, and by supersensitivity of post-synaptic 5-HT2A (and/or 5-HT2C) receptor-mediated secretion of hormones. Chronic exposure to SSRIs does not alter the neuroendocrine stress-response and produces inconsistent changes in alpha2 adrenoceptor-mediated GH secretion. Overall, the effects of SSRIs on neuroendocrine function are dependent on adaptive changes in specific neurotransmitter systems that regulate the secretion of specific hormones.
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PMID:Selective serotonin reuptake inhibitors and neuroendocrine function. 1050 38

The identification of the brain structures and neurotransmitters responsible for the generation and/or modulation of P300 could lead to important clinical implications. Since serotonin disturbances seem to play a critical role in depression, the aim of the study was to assess the possible relationships between the P300 event-related brain potential and serotonergic activity in depression. The study was conducted among 45 major depressive inpatients, and serotonergic activity was assessed by prolactin (PRL) response to flesinoxan (a 5-HT1A agonist). Results showed a significant negative correlation between P300 amplitude and PRL response to flesinoxan (r = -0.40, P = 0.007 at Cz; r = -0.47, P = 0.001 at Pz). In contrast, both P300 latency and reaction time were not related to endocrine response. This study supports a role for serotonin-1A in the neurobiological modulation of P300 amplitude.
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PMID:P300 event-related potential and serotonin-1A activity in depression. 1057 39

Serotonin, in addition to dopamine and other factors, is known to participate in the control of prolactin (PRL) and gonadotropins secretion. Isoteoline (IST), a putative serotonin antagonist and dopamine agonist, was studied for its neuroendocrine effects on PRL, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). IST was given intraperitoneally to adult male rats at doses of 0.25, 1 and 4 mg kg(-1)alone and 30 min prior to the injection of three 5-HT agonists with preferential affinity for various receptor subtypes: meta -chlorophenylpiperazine (m CPP) for 5-HT2C; 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) for 5-HT2A and 8-hydroxy-2-(di- n -propylamino)tetralin (8-OH-DPAT) for 5-HT1A. m CPP (2.5 mg kg(-1)), DOI (2.5 mg kg(-1)) and 8-OH-DPAT (1 mg kg(-1)) increased the serum PRL levels to a similar value, without affecting FSH and LH concentrations. IST by itself modified neither PRL nor gonadotropins serum levels. IST antagonized the m CPP-induced elevation in serum PRL, the lowest dose being the most effective. It had no effect on DOI and 8-OH-DPAT-induced increases of PRL levels and produced no significant changes in the gonadotropins levels when used as an antagonist. The results are discussed in terms of the likely involvement of serotonin vs dopamine mechanism in the effect of IST. It is concluded that the inhibition of the m CPP-induced rise of PRL levels by IST confirmed the serotonin antagonistic activity, previously demonstrated for this compound in other studies. The present results are also suggestive of possible selectivity of this antagonism of IST for the 5-HT2C vs 5-HT2A and 5-HT1A receptors, all of which are involved in the control of PRL secretion.
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PMID:Isoteoline, a putative serotonin antagonist, inhibits meta -chlorophenylpiperazine, but not 1-(2, -dimethoxy-4-iodphenyl)-2-aminopropane and 8-hydroxy-2-(di-n-propylamino)-tetraline-induced increase of serum prolactin levels. 1086 Jun 41

As a testable heuristic, the concept of stress response and adaptation is highly appealing, and the support for the concept is strong. This explanatory model of depression may account for hitherto apparently discordant facts--contradictory symptoms, antidepressant drugs that act on differing systems, facilitation of antidepressant response by augmentation, and response to psychotherapy and pharmacotherapy. This article has focused narrowly on specific cellular elements of the stress-adaptational mechanisms, including the AC-PKA and PLC-PKC transductional cascades, together with specific response elements, such as the HPA axis, BDNF, and NMDA receptors; however, other important mechanisms, including specific receptor subtypes (e.g., 5-HT1A and NE alpha 2), transmitter systems (e.g., acetylcholine and depamine), and hormones (e.g., thyroid and growth hormones and prolactin), which may be important, have not been discussed. As the complex interactions of these systems gradually yield to investigation, not only will new treatments be developed, but better matching of treatment to patient may become an achievable goal.
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PMID:Cellular mechanisms in the vulnerability to depression and response to antidepressants. 1114 43

We have studied the effect of acute and sub-chronic treatments of a formulation of a methanolic extract of hypericum perforatum (HP, also known as St John's wort) on plasma hormones and brain neurotransmitters in healthy human volunteers and rats. Also studied were the effects of equivalent acute doses of two constituents of HP (with respect to LI 160 extract), hypericin and hyperforin in rats. In acute treatment studies in normal volunteers subjects received 9 tablets of the finished product Jarsin 300 and placebo in the pilot study (unblinded) and in the main study (a double blind, balanced order, cross-over design). Results in normal volunteer studies show that HP caused significant increases of salivary cortisol and plasma growth hormone (GH) whereas it decreased plasma prolactin versus placebo. Plasma hormone levels were associated with a rise in plasma hyperforin but not with hypericin, however no significant correlation was found. In the animal studies, acute treatment with LI 160, hyperforin and hypericin all caused significant increases in plasma corticosterone. This was associated with significant increases in brain cortical tissue 5-HT content. The corticosterone responses were attenuated by the 5-HT2 receptor antagonist, ketanserin but not by the 5-HT1A antagonist, WAY-100635. This suggests that the corticosterone responses may be mediated via a 5-HT2 mechanism of action. When sub-chronic and acute treatment using two different doses of LI 160 were compared, plasma corticosterone level were significantly decreased. Thus suggesting a down-regulation or desensitisation of post-synaptic 5-HT2 receptors. Plasma prolactin was significantly reduced by acute treatment with LI 160 and hyperforin treatment but not by hypericin. This was associated with a concomitant rise in brain cortical tissue DA. Both LI 160 and hyperforin treatments decreased the plasma prolactin responses to the DA antagonist, haloperidol, suggesting that this may be associated with a DA-mediated mechanisn of action. When acute and sub-chronic treatments were compared, plasma prolactin responses were increased in the sub-chronically treated animals. The studies when taken together suggest that the LI 160 extract may effect plasma hormonal changes via both 5-HT and DA-mediated mechanisms but do not involve noradrenaline (NA). The data also suggests that hyperforin may be more important than hypericin for effecting these changes following acute treatment. Further studies investigating both acute and sub-chronic effects of these compounds are necessary.
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PMID:Researching the antidepressant actions of Hypericum perforatum (St. John's wort) in animals and man. 1151 72

Prolactin secretion is controlled by the hypothalamus through different neurotransmitters which interact with multiple receptor subtypes. The discovery of different families of receptors for serotonin (5-HT1-5-HT7) and excitatory aminoacids (NMDA, KA, AMPA and metabotropic receptors) ilustrates the complexity of this regulation. Moreover, in the rat the role of different neurotransmitters changes during pubertal development. Present experiments were carried out to analyse the interactions between AMPA and serotoninergic receptors in the control of prolactin secretion in prepubertal male rats. For this purpose, 16 and 23-day old male rats were treated with 5-hydroxytryptophan (5-HTP, precursor of serotonin synthesis) plus fluoxetine (blocker of serotonin reuptake), 8-OH-DPAT (agonist of 5-HT1A receptors), DOI and alpha-Me-5-HT (agonists of 5-HT2 receptors), 1-phenylbiguanide (agonist of 5-HT3 receptors) alone or in combination with AMPA (agonist of AMPA receptors). The results obtained indicate that: (a) activation of 5-HT1A receptors stimulated PRL secretion on day 16 and inhibited it on day 23; activation of 5-HT2 receptors stimulated PRL secretion on days 16 and 23, whereas activation of 5-HT3 receptors inhibited PRL release only on day 23; (b) activation of AMPA receptors inhibited PRL secretion on day 23, but not on day 16 and (c) a cross-talk is apparent between 5-HT2 and AMPA receptors in the regulation of PRL secretion, the stimulatory effect of DOI being blocked by AMPA.
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PMID:Interactions between serotoninergic and aminoacidergic pathways in the control of PRL secretion in prepubertal male rats. 1180 Feb 86

Typical antipsychotics (haloperidol) give rise to severe motor side-effects while atypical antipsychotics like clozapine do not. Action at several neurotransmitter receptors have been implicated. To identify the critical mechanisms involved we synthesized an 8-C1 isomer of clozapine which showed an equivalent affinity to clozapine on multiple receptors (5-HT1A, 5-HT2, D1, D4, M1) but differed in having a 10-fold higher affinity at the dopamine D2/3 receptor. When tested in a series of animal models indicative of the typical/atypical distinction (catalepsy, striatal gene-induction, prolactin elevation) isoclozapine lost atypical properties and behaved like a typical antipsychotic. Simultaneous in vivo receptor occupancy studies confirmed that alterations in D2 receptor occupancy were most closely related to loss of atypicality by clozapine's isomer isoclozapine. The implications for the design of future antipsychotics is discussed.
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PMID:Increasing D2 affinity results in the loss of clozapine's atypical antipsychotic action. 1199 96

The hypothermia produced by 5-HT1A agonists had initially been claimed to be caused by the activation of cell body 5-HT1A autoreceptors resulting in decreased 5-HT transmission in laboratory animals. In order to address this issue in humans, 12 healthy volunteers underwent a dietary tryptophan depletion paradigm to decrease 5-HT availability, under double-blind conditions, during which body temperature was monitored following oral administration of the 5-HT1A agonist buspirone (30 mg). In addition, plasma prolactin and growth hormone evaluations, two responses that are mediated via the direct activation of postsynaptic 5-HT1A receptors, were determined. The hypothesis was that if responses are mediated by decreased transmission at postsynaptic 5-HT1A receptors, resulting from dampened 5-HT release as a consequence of 5-HT1A autoreceptors activation, then responses to the exogenous 5-HT1A agonist should be attenuated when 5-HT availability has been markedly decreased beforehand. Buspirone produced the same significant increase in prolactin and growth hormone in the tryptophan-depleted state as in the control condition. Similarly, the degree of hypothermia produced by buspirone was not significantly different in the two experimental conditions. In conclusion, these results strongly suggest that the hypothermia and the increases in prolactin and growth hormone produced by buspirone are attributable to the enhanced activation of postsynaptic 5-HT1A receptors, and not to a decrease in 5-HT transmission resulting from the activation of the 5-HT1A cell body autoreceptors on 5-HT neurons.
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PMID:Serotonin 1A receptor activation and hypothermia in humans: lack of evidence for a presynaptic mediation. 1209 4

Dopamine is the primary inhibitory regulator of lactotroph proliferation and prolactin (PRL) secretion in vivo, acting via dopamine D2 receptors (short D2S and long D2L forms). In GH4C1 pituitary cells transfected with D2S or D2L receptor cDNA, dopamine inhibits PRL secretion and DNA synthesis. These actions were blocked by pertussis toxin, implicating G(i)/G(o) proteins. To address roles of specific G(i)/G(o)4 proteins in these actions a series of GH4C1 cell lines specifically depleted of individual Galpha subunits was examined. D2S-mediated inhibition of BayK8644-stimulated PRL secretion was primarily dependent on G(o) over G(i), as observed for BayK8644-induced calcium influx. By contrast, inhibitory coupling of the D2S receptor to TRH-induced PRL secretion was partially impaired by depletion of any single G protein, but especially G(i)3. Inhibitory coupling of D2L receptors to PRL secretion required G(o), but not G(i)2, muscarinic receptor coupling was resistant to depletion of any G(i)/G(o) protein, whereas the 5-HT1A and somatostatin receptors required G(i)2 or G(i)3 for coupling. The various receptors also demonstrated distinct G protein requirements for inhibition of DNA synthesis: depletion of any G(i)/G(o) subunit completely uncoupled the D2S receptor, the D2L receptor was uncoupled by depletion of G(i)2, and muscarinic and somatostatin receptors were resistant to depletion of G(i)2 only. These results demonstrate distinct receptor-G protein preferences for inhibition of TRH-induced PRL secretion and DNA synthesis.
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PMID:G protein preferences for dopamine D2 inhibition of prolactin secretion and DNA synthesis in GH4 pituitary cells. 1214 43

Serotonin has long been implicated as a key neurotransmitter in migraine. There is a dearth of research specifically examining 5-HT1A receptor sensitivity in migraine despite the importance of this receptor in regulating central serotonergic tone. In this study we examined the hypothesis that migraine without aura is associated with hypersensitivity of central 5-HT1A receptors, using a 5-HT1A neuroendocrine challenge drug and comparing serum prolactin responses between a test group with migraine and a matched group of healthy controls. Twelve female subjects fulfilling International Headache Society (IHS) criteria for migraine without aura were evaluated. Following an overnight fast, subjects presented for testing at 9am. An intravenous canula was inserted and serum prolactin was assessed at baseline and every 30 min for 3 h following a single dose of 30 mg oral buspirone, a 5-HT1A-receptor agonist. Subjects were assessed during the first 5 days of the menstrual cycle. No subjects were taking psychotropic medication or migraine prophylactic treatment. Patients with current or previous psychiatric disorder, daily headache or analgesic overuse were excluded. 16 healthy female volunteers matched for age and menstrual status were also evaluated and served as controls. There was no difference in baseline prolactin between groups. There was a significant rise in prolactin following buspirone in both groups. Subjects with migraine had a significantly increased prolactin response to buspirone (delta max) compared to controls (P < 0.001). This study supports the hypothesis that migraine without aura is associated with a relative hypersensitivity of central 5-HT1A receptors. This is of relevance given the role of the 5-HT1A receptor in controlling raphe 5-HT tone and in the possible association between migraine and anxiety and depression.
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PMID:Central 5-HT receptor hypersensitivity in migraine without aura. 1515 63


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