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)

The role of 5-hydroxytryptamine (5-HT), its enteric locus of action, and receptor subtypes involved in the regulation of jejunal contractions were investigated by close intra-arterial infusions in conscious dogs. Close intra-arterial infusions of 5-HT in short segments of the jejunum stimulated phasic contractions that were blocked completely by atropine, partially by tetrodotoxin, and not affected by hexamethonium. This response was also blocked significantly by 5-HT2A and 5-HT2C receptor antagonists but was not affected by 5-HT1A/5-HT1B, 5-HT3, and 5-HT4 receptor antagonists. Spontaneous phase III contractions were inhibited significantly by 5-HT2A and 5-HT2C receptor antagonists, not affected by 5-HT1A/5-HT1B and 5-HT3 receptor antagonists, and enhanced by 5-HT4 receptor antagonists. Repeated close intra-arterial infusions of 5-HT over several days stimulated giant migrating contractions. We conclude that in the conscious state, 5-HT acts on 5-HT2A and 5-HT2C receptors located on postsynaptic cholinergic neurons in the canine jejunum to stimulate phasic contractions and phase III activity. The 5-HT4 receptors in the canine small intestine may be localized on nonadrenergic, noncholinergic inhibitory neurons; these receptors suppress the amplitude and duration of phase III activity.
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PMID:5-HT-induced jejunal motor activity: enteric locus of action and receptor subtypes. 876 7

The hyposecretion of growth hormone (GH) in maternal separation (MS) of rat pups is remarkably similar to the specific suppression of GH secretion to evocative tests in infants diagnosed with Reactive Attachment Disorder of Infancy (RADI). Growth hormone-releasing factor (GRF) and somatostatin (SS) provide opposing regulation of GH secretion, and both are modified by noradrenergic and serotonergic stimuli in neonatal and adult rats. In this study, GRF administration reversed MS-induced suppression of GH secretion in 10-day-old pups, but this action of GRF was prevented by pretreatment with cyproheptadine (Cypro), a serotonergic antagonist. The normalization of GH secretion after return to the dam was not altered by pretreatment with SS. Indirect 5-HT agonists, fluoxetine (FLX) and 5-HTP, both stimulated GH secretion in 10-day-old pups. All mixed serotonin- and 5-HT1A-receptor agonists suppressed GH secretion in 10-day-old pups. Antagonists Cypro and ketanserin (Ket) suppressed FLX-induced GH secretion. In contrast, only Cypro suppressed 5-HTP-induced GH secretion. Maternal separation inhibited GH secretion stimulated by 5-HTP, but not by FLX. The serotonergic pathway acting on 5-HT2A receptors may be obligatory for GRF-mediated stimulation and is sensitive to inhibition by Cypro. In addition, a Ket-sensitive serotonergic parallel pathway acting on 5-HT2C receptors may also stimulate GH secretion by acting on GRF or SS. However, only the obligate 5-HT2A pathway appears to be suppressed in MS. These data and observations by others indicate that specific suppression of GH secretion in MS may derive from a reduction in GRF release through noradrenergic neurons, possibly impinging upon serotonergic terminals in the hypothalamus. This study may also provide insight into mechanisms by which GH secretion is suppressed in humans with RADI.
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PMID:Inhibition of GH in maternal separation may be mediated through altered serotonergic activity at 5-HT2A and 5-HT2C receptors. 877 64

Studies in which serotonergic drugs were administered either systemically or directly into central sites have implicated 5-HT in the inhibitory control of feeding in mammals. In animal models and in humans, 5-HT agonists such as fenfluramine, fluoxetine and sertraline reduced the rate of eating and the size of meals in a manner suggesting that increasing serotonergic neurotransmission specifically enhanced satiation. In rodents, directly acting agonists at 5-HT1B, 5-HT2C or 5-HT2A receptors decreased food intake but by different behavioral mechanisms. Stimulation of the 1B and 2C subtypes may probe physiological roles in feeding and satiety. The former receptors may be involved primarily in regulating meal size and the latter more in controlling eating rate. Activation of both may be required for complete expression of behavioral satiety. By contrast, stimulating 2A sites may simply disrupt the continuity of feeding. Drugs that stimulate 5-HT1A autoreceptors increase food intake, presumably by acutely reducing the firing of serotonergic neurons in the brain. The hypothalamic paraventricular nucleus (PVN) has been proposed as an important terminal field in the forebrain that is involved in 5-HT's satiety role although recent studies implicate extra-PVN regions in this function. Peripherally administered 5-HT also decreases food intake in rats in a behaviorally specific manner. Studies with antagonists and with structural analogs of 5-HT revealed that 5-HT's peripheral satiety action involves 5-HT1-like and 5-HT2-like mechanisms. Thus, within and outside the brain, multiple pharmacological and behavioral mechanisms contribute to serotonergic functions in ingestion. The rich body of data from preclinical investigation in animals provides the foundation for therapeutic development in humans.
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PMID:Serotonergic control of the organization of feeding and satiety. 878 74

Drugs that enhance brain serotonin function (direct agonists, serotonin uptake inhibitors and serotonin releasers) increase serum corticosterone concentration in rats, and in many cases ACTH has been shown to be similarly increased. At least two distinct serotonin receptor subtypes can mediate this effect. One is the 5-HT1A receptor, and the other seems to be a 5-HT2A receptor. Possibly, the 5-HT2C receptor or other receptors can also mediate these effects. The increase in serum corticosterone seems to be one useful marker in characterizing drug effects on serotonergic function. Much needs to be learned about the physiological importance and roles of this serotonergic influence on pituitary-adrenocortical function. Some studies have suggested it may be important in the diurnal rhythmicity of glucocorticoid secretion and perhaps in some stress effects. Serotonergic activation can also increase plasma levels of ACTH and cortisol in humans. Although the effects in humans are less well characterized than in rats, they seem to be useful as a way of probing brain serotonergic function in disease or after drug treatment. As more drugs that act selectively on a single receptor subtype become available for use in humans, more precise information about particular receptor subtypes should be attainable.
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PMID:Serotonin receptors involved in regulation of pituitary-adrenocortical function in rats. 878 5

This work examines the autoradiographic distribution of serotonin (5-HT) receptor subtypes in rat, guinea pig and human brain, using [3H]5-HT and [3H]5-CT as ligands. Different displacers were used to mask radioligand binding to 5-HT1A, 5-HT1B/1D and 5-HT2C receptors, in an attempt to visualize other receptor populations, which presumably would correspond to 5-HT1E and 5-HT1F sites. Brain areas enriched in 5-HTnon1A/1B/1D sites in guinea pig were the hilus, dentate gyrus, striatum, claustrum, substantia nigra and superior colliculus, among others. In humans, however, the claustrum, a structure supposed to contain 5-HT1E sites, showed significant densities of [3H]5-CT binding. An interesting finding was that blockade [3H]5-CT binding to 5-HT1A receptors by 8-OH-DPAT could only be achieved at very high concentrations of the displacer. This could be due to differences in the affinity of ligands in intact tissue sections compared to membrane homogenates or cell lines. Another possibility would be that [3H]5-CT labels 5-HT1A receptors in the low-affinity state. These hypotheses remain to be investigated.
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PMID:Autoradiographic analysis of 5-HT receptor subtypes labeled by [3H]5-CT ([3H]5-carboxamidotryptamine). 878 10

To test the hypothesis that the mechanisms of 5-HT1 and 5-HT2 receptor-mediated hormonal responses are different, we compared the effects of hypothalamic paraventricular nucleus (PVN) lesions on the ACTH/corticosterone, prolactin and oxytocin responses to the 5-HT1A agonist ipsapirone (1 and 2 mg/kg), the 5-HT2C agonist m-chlorophenylpiperazine (m-CPP, 0.6 mg/kg), which also binds to other 5-HT receptors with lower affinity, and the 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 1 mg/kg) in chronically cannulated, freely moving male rats. Pharmacological characterization using antagonists with different affinity for 5-HT2A and 5-HT2C receptors revealed that DOI's responses were mediated mainly by 5-HT2A receptors and m-CPP's responses were almost exclusively mediated by 5-HT2C receptors. ACTH/corticosterone responses to ipsapirone, DOI and m-CPP were almost completely blocked after PVN lesions. Prolactin responses were significantly different in lesioned rats only after DOI and m-CPP challenges. Oxytocin responses to ipsapirone and DOI, but not m-CPP were markedly attenuated after PVN lesions. The present findings suggest that the PVN, or neural pathways close to it, mediate corticosterone and in some cases prolactin and oxytocin responses to selective stimulation of 5-HT1A, 5-HT2A, or 5-HT2C receptors.
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PMID:Role of the hypothalamic paraventricular nucleus in 5-HT1A, 5-HT2A and 5-HT2C receptor-mediated oxytocin, prolactin and ACTH/corticosterone responses. 878 18

We evaluated the effects of two drugs active at serotonin receptors, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a 5-HT1A agonist) and N-3-trifluoromethylphenyl)piperazine hydrochloride (TFMPP, a 5-HT2C agonist) on learning using a novel water maze previously characterized in our laboratory. The water maze utilized is a traditional type of maze with alleyways and doors through which the rats learn to swim to reach a platform, unlike the open pool Morris water maze task. Performance is assessed by swim time required to reach the platform and errors committed. Following initial training on maze configuration A, rats were assigned to saline, TFMPP and 8-OH-DPAT treatment groups and tested for performance once per dose, 30 min after administration of drug (0.25, 0.5, and 1.0 mg/kg IP). Swim times were significantly increased as compared to saline for all doses for both drugs. The error rate was increased for 8-OH-DPAT at all doses, while TFMPP had no effect on error rate at any dose. Next, rats were challenged to learn new mazes following daily administration of 0.25 or 0.5 mg/kg of each drug 30 min prior to each daily swim trial. Rats given 0.25 mg/kg of 8-OH-DPAT learned new maze C more slowly than saline-treated rats, while TFMPP had no effect at this dose. At the higher dose of 0.5 mg/kg, tested on new maze B, TFMPP administration significantly increased swim times but not errors, while this dose of 8-OH-DPAT markedly increased both swim time and errors. Finally, rats from all groups were tested on maze E after drug administration was discontinued, and there were no performance differences among groups. These data suggest that serotonin1A receptors may inhibit learning.
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PMID:Effects of the serotonin receptor agonists 8-OH-DPAT and TFMPP on learning as assessed using a novel water maze. 880 48

Malfunction of the serotonergic system and dysregulation of the hypothalamo-pituitary-adrenocortical axis have been implicated in the pathophysiology of depression. Several studies provide evidence for reciprocal influences between glucocorticoids and 5-HT receptors. The effect of repeated treatment with a high dose of corticosterone (50 mg/kg s.c. twice daily for 4 days) on 5-HT receptor subtype-mediated behaviours was studied. It was found that in rats that were repeatedly treated with corticosterone the number of 2-chloro-6-(1-piperazinyl)pyrazine HCl (MK 212)-induced, 5-HT2C receptor-mediated penile erections were reduced, whereas both MK 212 and (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced 5-HT2A receptor-mediated head shakes were increased. The (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)-induced lower lip retraction mediated by presynaptic 5-HT1A receptors was unchanged, whereas the open field activity induced by 8-OH-DPAT was enhanced in corticosterone pretreated rats. These changes in 5-HT receptor subtype-mediated behaviours were not seen after a single injection with corticosterone given 24 h or 5 days before. The results suggest that 5-HT2A, 5-HT2C and postsynaptic 5-HT1A receptor-mediated behaviour can be modulated by repeated treatment with a high dose of corticosterone.
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PMID:Modulation of 5-HT receptor subtype-mediated behaviours by corticosterone. 884 Jan 20

While serotonin has been shown to play an important role in peripheral pain mechanisms, the specific subtypes of receptors involved and their differential distribution between the sensory and sympathetic nervous system remains poorly understood. In this study, the presence of messenger RNA for rat serotonin receptor subtypes in peripheral sensory and sympathetic ganglia was detected using the method of polymerase chain reaction. Lumbar dorsal root ganglia, superior cervical sympathetic ganglia and lumbar sympathetic ganglia were excised from anesthetized Sprague-Dawley rats. Oligonucleotide primers were chosen based on unique regions of complementary DNA sequence for each of the 12 cloned rat serotonin receptor subtypes (i.e. 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT5A, 5-HT5B, 5-HT6 and 5-HT7) and high stringency conditions were used during polymerase chain reaction. Within lumbar dorsal root ganglia, the presence of the 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2C, 5-HT3 and 5-HT7 receptor subtype messenger RNAs was detected. Within superior cervical ganglia, the presence of messenger RNA for 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT3, 5-HT6, and 5-HT7 receptor subtypes was detected. Lumbar sympathetic ganglia displayed banding identical to the superior cervical ganglia with the exception of the 5-HT6 receptor which was not detected in the lumbar sympathetic ganglia. The polymerase chain reaction product from each positively-detected receptor subtype was subcloned and sequenced and found to correspond to published complementary DNA sequences. Findings from this study may direct further efforts to determine the role of 5-hydroxytryptamine receptors in the peripheral nervous system.
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PMID:5-Hydroxytryptamine receptor subtype messenger RNAs in rat peripheral sensory and sympathetic ganglia: a polymerase chain reaction study. 884 58

A pharmacologic analysis of the discriminative stimulus of metachlorophenylpiperazine (mCPP) is reported. mCPP and m-trifluoromethylphenylpiperazine generalised, whereas 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole, 6-chloro-2-(1-piperazinyl)-pyrazine, and mesulergine partially generalised to the mCPP discriminative cue. However, although mianserin, methiothepin, ritanserin, mesulergine and N-(1-methyl-5'-indolyl)-N'-(3-pyridyl)urea hydrochloride (SB 200646) all antagonised the effect of 5-hydroxytryptamine (5-HT) on IP3 formation in the rat choroid plexus, they failed to antagonise the mCPP response in the drug discrimination studies. The 5-HT3 receptor antagonist MDL 72222 neither generalised nor antagonised the mCPP cue. These data suggest that neither the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT5, 5-HT6, nor 5-HT7 receptors are involved. The response does appear to be mediated by a postsynaptic 5-HT receptor, however, because fenfluramine generalised to the cue. Haloperidol generalises, and amphetamine partially antagonises the mCPP discriminative cue and low doses of apomorphine partially generalises to the mCPP cue, which suggests that a decrease in dopamine neurotransmission may also be involved.
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PMID:Pharmacologic evaluation of the discriminative stimulus of metachlorophenylpiperazine. 884 38


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