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)

This study was performed in rats to determine if serotonin and its receptors are involved in the increase of gastric emptying (GE) induced by benzodiazepine (BZ) withdrawal. GE was measured with a test meal (2 ml) containing 1 microCi/ml of 51Cr sodium chromate administered in rats, either previously receiving injections with diazepam (15 mg/kg/day i.p.) or with DMSO (0.9 ml/day i.p.) during 7 days. On the 8th day, animals received the different serotonin (5-HT) agonists or antagonists, and flumazenil (BZ antagonist; 15 mg/kg i.p.) 30 and 15 min, respectively, before the test meal. Methiotepin (5-HT1 antagonist) either i.p. (0.1-1 mg/kg) or intracerebroventricularly (10 micrograms/kg) had no effect on the increase of GE induced by precipitated-withdrawal. 8-OH-DPAT (5-HT1A agonist) administered i.c.v. (1-10 micrograms/kg) dose dependently reduced GE increase. Administered i.p. (0.1 mg/kg), it blocked GE increase in control and diazepam-withdrawn rats. Ritanserin (5-HT2 antagonist) antagonized GE increase only when administered i.p. (0.1 mg/kg). Granisetron (5-HT3 antagonist) was active both i.p. (0.01-0.1 mg/kg) and intracerebroventricularly (1-10 micrograms/kg). Administered intracerebroventricularly (1 microgram/kg) in diazepam-treated rats, 5-HTP mimicked the effect of flumazenil. It is concluded that diazepam-withdrawal increases GE by stimulating central release of 5-HT and/or central activation of 5-HT neurons. At least central 5-HT3 receptors, and in less extend, peripheral 5-HT2 receptors are involved in this mechanism.
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PMID:Benzodiazepine-withdrawal-induced gastric emptying disturbances in rats: evidence for serotonin receptor involvement. 779 Nov 33

The purpose of this study was to develop a radiopharmaceutical that could be used to selectively image 5-HT1A receptors with positron emission tomography (PET). No-carrier-added 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[18F] fluorobenzamido]ethylpiperazine (p-[18F]-MPPF, 2) was synthesized by the nucleophilic substitution of the corresponding nitro precursor 1 with K[18F]/Kryptofix 2.2.2. in dimethyl sulfoxide (DMSO) at 140 degrees C for 20 min followed by purification with high-performance liquid chromatography (HPLC) in 10% yield in a synthesis time of 90 min from end of bombardment (EOB). Specific activity was 1-4 Ci/microM. Biodistribution studies in rats showed that the initial uptake of 2 in the brain was high (0.7% dose/g tissue at 2 min). It was then rapidly eliminated. Rates of elimination were significantly slower in brain regions with high concentrations of 5-HT1A receptors (hippocampus, cortex, and hypothalamus) than in control regions. The maximum hippocampal/cerebellar ratio was 5.6:1 at 30 min postinjection. Uptake values in serotonergic, but not in control, regions were significantly reduced by prior treatment with either (+/-)-8-OH-DPAT (2 mg/kg, i.v., 5 min prior) or WAY 100635 (1 mg/kg, i.v., 5 min prior). Radioactivity in the femur did not increase with time, suggesting that in vivo defluorination may not be the major route of metabol sm. PET studies of 2 in a monkey demonstrated selective uptake and retention of 2 in the hippocampus. The hippocampal/cerebellar ratio was 3:1 at 30 min postinjection. The ratio was reduced to 1:1 by administering (+/-)-8-OH-DPAT (2 mg/kg, i.v.) 23 min postinjection of 2. Analyses of arterial plasma by HPLC revealed that 20% of radioactivity in the plasma remained as the parent compound 2 at 30 min postinjection. The results suggest that p-[18F]-MPPF may be a useful radioligand for studying cerebral 5-HT1A receptors in humans with PET techniques.
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PMID:P-[18F]-MPPF: a potential radioligand for PET studies of 5-HT1A receptors in humans. 902 95

Rats implanted bilaterally with cannulae in the entorhinal or posterior parietal cortex or in the amygdaloid nucleus were trained in one-trial step-down inhibitory (passive) avoidance using a 0.3 mA footshock. At 0, 3, 6 or 9 h after training, they received localized 0.5 microliter infusions into these areas of a vehicle, or of 8-Br-cAMP, forskolin (adenylyl cyclase activator), KT5720 (protein kinase A inhibitor), SKF38393 (dopamine D1 receptor agonist), SCH23390 (D1 antagonist), norepinephrine hydrochloride, timolol hydrochloride (beta blocker), 8-HO-DPAT (5-HT1A receptor agonist) or NAN-190 (5-HT1A antagonist) dissolved in 20% dimethylsulfoxide (DMSO) in saline (vehicle). Rats were tested for retention 24 h after training. 8-Br-cAMP, forskolin, SKF 38393 and norepinephrine caused memory facilitation and KT5720, SCH23390, timolol and 8-HO-DPAT caused retrograde amnesia when given into the entorhinal cortex 0, 3 or 6 h but not 9 h after training. When given into the posterior parietal cortex 0, 3 or 6 but not 9 h after training, KT5720 was amnestic. When given into this structure 3 or 6 h but not 0 or 9 h after training 8-Br-cAMP, forskolin and norepinephrine caused memory facilitation and KT5720, SCH23390 and timolol caused retrograde amnesia. All treatments given into the amygdala 0, 3 or 6 h after training were ineffective except for norepinephrine given at 0 h, which caused facilitation. The data point to a role of cAMP/protein kinase A-dependent mechanisms in memory formation in the entorhinal and parietal cortex, but not the amygdala, from 0 to 6 h after training, and to a strong modulation of these mechanisms by dopaminergic D1, beta-noradrenergic and 5-HT1A receptors. The lack of effect of NAN-190 but not 8-HO-DPAT in both cortical regions suggests that 5-HT1A receptors do not play a physiological role but can be activated pharmacologically. The fact that SCH23390 was amnestic but SKF38393 had no effect when given into the parietal cortex suggests that D1 receptors may play a maintenance rather than a stimulant role in this area.
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PMID:Late and prolonged post-training memory modulation in entorhinal and parietal cortex by drugs acting on the cAMP/protein kinase A signalling pathway. 983 61

5-hydroxytryptamine receptors 2A and 1A (5-HT2A and 5-HT1A receptors) are most closely related to anxiety-like behavior in post-traumatic stress disorder. This study was aimed at determining how 5-HT2A and 5-HT1A receptors mediate stress-induced anxiety-like behavior. C57BL/6 mice were exposed to conditioned fear stress combined with single-prolonged stress and injected with corresponding antagonists of 5-HT2A or 5-HT1A receptors or DMSO. The established mouse model was used in conjunction with open-field test, freezing behavioral test and elevated plus maze test. Protein expression levels of 5-HT2A and 5-HT1A receptors, ERK1 and ERK2, pERK1, pERK2 and c-Myc in mice hippocampus were evaluated by Western blot analysis and immunofluorescence labeling. Relative mRNA expression levels of 5-HT2A and 5-HT1A receptors, ERK1, ERK2 and c-Myc were analyzed with RT-qRCR. 5-HT2A receptor plays a significant role in anxiety-like behavior by inhibiting 5-HT1A receptor expression. Effect of 5-HT2A and 5-HT1A receptors on stress-related anxiety-like behavior was elicited via ERK1 and ERK2 phosphorylation. On the basis of our experimental results, we hypothesize interaction between 5-HT2A and 5-HT1A receptors in mouse hippocampus to mediate anxiety-like behavior via ERK pathway.
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PMID:Serotonin receptors 2A and 1A modulate anxiety-like behavior in post-traumatic stress disordered mice. 3110 36