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 effects of the Ca2+ and 5-HT1 and 5-HT2 receptor antagonist dotarizine and of some other agonists and antagonists of different 5-HT receptor subtypes administered alone or in combination with the 5-HT uptake inhibitor fluoxetine (FLU) on nociception were studied, using a foot-pressure method (analgesy-meter testing). Dotarizine (DOT) administered at a dose of 50 mg/kg for 3 days orally significantly increased the pain threshold. Fluoxetine (FLU) administered at a dose of 10 mg/kg for 3 days also significantly increased the pain threshold. The combination of DOT and FLU abolished the analgesic effects of the two drugs. The 5-HT1A and 5-HT1B/1C receptor agonists buspirone and m-CPP decreased the pain threshold. The antagonists of 5-HT1A(NAN-190),5-HT1/5-HT2(methysergide), 5-HT2 (ritanserin), and 5-HT3 (ondansetron) receptors as well as the agonists of 5-HT2(DOI) and 5-HT3 (mCPBG) receptors increased the pain threshold. Fluoxetine at a single dose of 10 mg/kg differently influenced the effects of the 5-HT agonists and antagonists on nociception. Comparison of the effects of dotarizine with the effects of some of the agonists and antagonists of 5-HT receptor subtypes on the nociceptive and other actions suggests the possibility of a therapeutic value of dotarizine as an antimigraine drug.
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PMID:Effects on nociception of the Ca2+ and 5-HT antagonist dotarizine and other 5-HT receptor agonists and antagonists. 883 Aug 81

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

The effects of drugs selectively effecting central serotonergic systems on immobilization-induced analgesia (SIA) were tested in the rat. The drugs were used in dose ranges previously shown to effect emotional processes. SIA was tested using the tail withdrawal method. It was found that pretreatment of rats with para-chlorophenylalanine (p-CPA), an inhibitor of serotonin synthesis, significantly attenuated SIA, measured immediately after stress session. Ritanserin, a 5-HT2A/2C receptor antagonist, ondansetron, a 5-HT3 receptor antagonist and citalopram, a selective serotonin re-uptake blocker increased the baseline pain threshold, whereas 8-OH-DPAT, a full 5-HT1A receptor agonist and buspirone, a partial 5-HT1A receptor agonist expressing also high affinity towards dopaminergic D2 receptors, were without effect on pain perception and stress induced analgesia. It has been concluded, that modification of SIA by serotonergic drugs probably merely reflects changes in the activity of the 5-HT system on the spinal cord level, with minor, if any, contribution of supraspinal emotional centers.
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PMID:Influence of serotonergic drugs on restraint stress induced analgesia. 886 28

Social conflict between mice produces analgesia in the attacked mouse. Both the magnitude and type (opioid or nonopioid) of this analgesia have been related to attack intensity and strain of mouse. In the present study low intensity social conflict (7 bites) did not produce analgesia, whereas high intensity - 30 and 60 bites - interactions produced, respectively, short-lasting (5 min) and very short-lasting (1 min) analgesia in Swiss albino mice, when compared with nonaggressive interaction (0 bite). The 30 bites aggressive interaction induced analgesia (AIIA) was not affected by IP injection of either naloxone (5.0 and 7.5 mg/kg) or diazepam (0.5, 1.0, 2.0 and 4.0 mg/kg). However, this attack-induced analgesia was reduced after IP administration of the 5-HT1A agonists, gepirone (0.3 and 3.0 mg/kg) and BAY R 1531 (0.01 mg/kg). These results indicate that the analgesia induced by 30 bites social conflict in Swiss albino mice does not involve opioid and GABA-benzodiazepine (GABA-BZD) mechanisms. In addition, they suggest that high-intensity social conflict activates serotonergic pain modulatory systems that act through 5-HT1A receptors.
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PMID:High intensity social conflict in the Swiss albino mouse induces analgesia modulated by 5-HT1A receptors. 907 86

The primary sensory Rohon-Beard (R-B) neurons of Xenopus larvae are highly analogous to the C fibers of the mammalian pain pathway. We explored the actions of 5-HT by studying the modulation of Ca2+ currents. In approximately 80% of the acutely isolated R-B neurons, 5-HT inhibited the high voltage-activated (HVA) currents by 16% (n = 29) and the T-type currents by 24% (n = 41). The modulation of the T-type and the HVA currents was mimicked by selective 5-HT1A and 5-HT1D agonists: 8-OH-DPAT and L-694,247. The effects of the agonists were blocked by their respective 5-HT1A or 5-HT1D antagonists: p-MPPI and GR127935, suggesting that both 5-HT1A and 5-HT1D receptors were involved. Approximately 70% of the actions of 5-HT on HVA currents was occluded by omega-conotoxin-GVIA (N-type channel blocker), whereas the rest of the modulation ( approximately 30%) was occluded by <100 nM omega-agatoxin-TK (P/Q-type channel blocker). This suggests that 5-HT acts on N- and P/Q-type Ca2+ channels. Neither the modulation of the T-type nor that of the HVA currents was accompanied by changes in their voltage-dependent kinetics. Cell-attached patch-clamp recordings suggest that the modulation of the T-type channel occurs through a membrane-delimited second messenger. We have studied the functional consequences of the modulation of T-type Ca2+ channels and have found that these channels play a role in spike initiation in R-B neurons. Modulation of T-type channels by 5-HT therefore could modulate the sensitivity of this sensory pathway by increasing the thresholds of R-B neurons. This is a new and potentially important locus for modulation of sensory pathways in vertebrates.
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PMID:Serotonergic inhibition of the T-type and high voltage-activated Ca2+ currents in the primary sensory neurons of Xenopus larvae. 927 19

Although serotonin has been shown to play an important role in peripheral pain mechanisms, the specific subtypes of serotonin receptors involved in pain and hyperalgesia remain poorly understood. To date, no previous study has attempted to determine the presence of any serotonin receptor subtype in human dorsal root ganglia. In this study, the presence of messenger RNA for eight human serotonin receptor subtypes in lumbar dorsal root ganglia was detected using the method of polymerase chain reaction. Dorsal root ganglia were excised post mortem from four patients. Oligonucleotide primers were chosen based on unique regions of complimentary DNA sequence for eight cloned human serotonin receptor subtypes (i.e. 5-HT1A, 5-HT1D alpha, 5-HT1D beta, 5-HT1E, 5-HT1F, 5-HT2A, 5-HT2C and 5-HT7). The presence of 5-HT1D alpha, 5-HT1D beta, 5-HT1E, 5-HT1F, 5-HT2A and 5-HT7 receptor subtype messenger RNA was detected in dorsal root ganglia from three of the four subjects. 5-HT1A receptor subtype messenger RNA was detected in one of the four subjects. No 5-HT2C receptor subtype messenger RNA could be detected. Findings from this study may direct further efforts to determine the role of serotonin receptors in the peripheral nervous system.
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PMID:5-Hydroxytryptamine receptor subtype messenger RNAs in human dorsal root ganglia: a polymerase chain reaction study. 931 30

Involvement of the cerebral serotoninergic system has been invoked to explain the origin of the pain and the vascular phenomena in migraine. To further investigate the type of cerebral serotonin receptors that may be altered in migraine, the prolactin (PRL) and cortisol responses to m-chlorophenylpiperazine (mCPP), a selective 5-HT1A,-5-HT(2A/C) receptor agonist, were monitored in 12 patients suffering from migraine without aura and in 14 matched healthy controls. Each subject underwent two challenges, one with mCPP (0.5 mg/kg) and the other with placebo (orally) using a double-blind crossover design. Anxiety level was measured by the State Trait Anxiety Inventory. Migraine patients had a greater PRL response to mCPP (p = 0.05) and greater anxiety (p < 0.01) than controls; cortisol response to mCPP did not differ suggesting that 5-HT2C receptors are normal in migraine. Augmented PRL response to mCPP could derive from 5-HT1A receptor hypersensitivity, perhaps as as a consequence of anxiety due to pain expectation. Cerebral 5-HT1A hypersensitivity could also explain the increased occurrence of migraine attacks during anxiety.
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PMID:5-HT1A receptor hypersensitivity in migraine is suggested by the m-chlorophenylpiperazine test. 972 41

Systemic administration of sumatriptan and buspirone (20 mg/kg: 5-HT1A agonists) produced antinociception against acetic acid-induced writhing. The antinociceptive effect was potentiated by cholinomimetic physostigmine (0.05 mg/kg i.p.) and blocked by the muscarinic antagonist atropine (5 mg/kg i.p.). Naloxone, an opiate antagonist, failed to reverse the sumatriptan- or buspirone-induced antinociception, but pindolol (10 mg/kg), a nonselective 5-HT1A antagonist, blocked this response. Sumatriptan- or buspirone-induced antinociception was significantly potentiated by L-NAME (a nitric oxide [NO] synthase inhibitor) although L-NAME (20 mg/kg) given alone had no effect on the nociceptive threshold. Recent studies have suggested that the L-arginine/NO/cGMP pathway is involved in the modulation of pain perception. The present results suggest that NO may play a role in cholinergic antinociception-mediated 5-HT1A receptor stimulation and that NO exerts an inhibitory action on cholinergic analgesia.
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PMID:L-NAME, a nitric oxide synthase inhibitor, modulates cholinergic antinociception. 1038 17

Single unit extracellular recordings from the dorsal horn neurons were obtained with glass micropipettes in pentobarbital-anesthetized rats. A total of 115 wide dynamic range (WDR) neurons were studied in 94 rats. In normal rats, the size of nociceptive receptive fields (RFs) of WDR neurons was approximately 123.3 +/- 8.21 mm2 (n = 88). Following carrageenan-induced inflammation, the RFs were markedly enlarged (332.4 +/- 30.1 mm2, n = 27, P < 0.001). The frequency of background activity of the WDR neurons in carrageenan-injected rats (11.3 +/- 2.1 imp/s, n = 27) was greater than that in normal rats (7.1 +/- 0.8 imp/s, n = 88, P < 0.05). In 82% of WDR neurons in normal rats, there was a separation between the A- and C-responses. In contrast, in 67% of the neurons in carrageenan-injected rats, the response to suprathreshold electrical stimuli was a long train with no separation between the A- and C-responses. In carrageenan-injected rats, the magnitude and duration of the nociceptive responses were significantly increased compared to those in normal rats, and the average C-response threshold (7.7 +/- 1.1 mA, n = 27) was lower than that in normal rats (10.4 +/- 0.7 mA, n = 88, P < 0.05). Intrathecal injection of the 5-hydroxytryptamine(1A) (5-HT1A) receptor agonist 8-hydroxy-DPAT hydroxybromide (8-OH-DPAT) (0.305, 1.525, 3.05, and 15.25 mM) dose-dependently increased Adelta- and C-responses and post-discharge in most of the WDR neurons. Following carrageenan-induced inflammation, the 8-OH-DPAT-induced facilitatory effect on Adelta- and C-responses and post-discharge was significantly enhanced (P < 0.05). Intrathecal injection of the 5-hydroxytryptamine1B (5-HT1) receptor agonist CGS12066A (0.222, 1.11, 2.22, and 11.1 mM) dose-dependently enhanced the C-response and post-discharge without influencing the Adelta-response. In carrageenan-injected rats, CGS12066A not only enhanced the facilitatory effect on the C-response and post-discharge, but also facilitated the Adelta-response. Intrathecal injection of the 5-HT(1A) receptor antagonist NAN-190 (0.2 mM) alone did not influence Adelta- and C-responses and post-discharge of WDR neurons in normal rats. When 0.2 mM NAN-190 was co-administered with 3.05 mM 8-OH-DPAT, the facilitatory effect of 8-OH-DPAT on Adelta- and C-responses and post-discharge was completely antagonized, whereas CGS12066A-induced facilitation on the C-response and post-discharge was not influenced by co-administration of 0.2 mM NAN-190 and CGS12066A. These data suggest that 5-HT1A and 5-HT1B receptor subtypes mediate the facilitatory effect of 5-HT on nociceptive processing in the spinal cord of rats. The excitability of dorsal horn WDR neurons and the sensitivity of the neurons to intrathecal 5-HT1A and 5-HT1B receptor agonists might increase following carrageenan-induced inflammation.
Pain 2001 May
PMID:The role of 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptors in modulating spinal nociceptive transmission in normal and carrageenan-injected rats. 1132 41

The experiments examined antinociceptive and intrinsic behavioral effects induced by the prototypical 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-[di-n-propylamino] tetralin) in rats. 8-OH-DPAT (0.01-2.5 mg/kg, subcutaneous (s.c.)) reduced both the paw licking and paw elevation induced by (2.5%) formalin injection into the plantar surface of the right hindpaw; it also produced forepaw treading. All of these effects were completely blocked by pretreatment with WAY 100635 (N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride) (0.16 mg/kg, s.c.); prazosin (0.63 mg/kg, s.c.) inhibited forepaw treading, but not 8-OH-DPAT's action on paw elevation and paw licking. Repeated injection of 8-OH-DPAT (0.63 mg/kg, s.c.) twice daily for 4 days, markedly reduced 8-OH-DPAT's ability to produce forepaw treading, but exerted only little and inconsistent effects on its paw licking and paw elevation-inhibiting action. The data indicate that 8-OH-DPAT exerts an analgesic action in the formalin model of tonic nociceptive pain; this action is mediated by 5-HT(1A) receptors, and is not confounded by the productive sign (i.e., forepaw treading) of the 5-HT syndrome which 8-OH-DPAT also induces.
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PMID:In the formalin model of tonic nociceptive pain, 8-OH-DPAT produces 5-HT1A receptor-mediated, behaviorally specific analgesia. 1139 66


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