Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Excised outside-out patches from HEK293 cells stably transfected with the human (h) 5-HT3A receptor cDNA were used to determine the effects of cannabinoid receptor ligands on the 5-HT-induced current using the patch clamp technique. In addition, binding studies with radioligands for 5-HT3 as well as for cannabinoid CB1 and CB2 receptors were carried out. The 5-HT-induced current was inhibited by the following cannabinoid receptor agonists (at decreasing order of potency): 9-THC, WIN55,212-2, anandamide, JWH-015 and CP55940. The WIN55,212-2-induced inhibition was not altered by SR141716A, a CB1 receptor antagonist. WIN55,212-3, an enantiomer of WIN55,212-2, did not affect the 5-HT-induced current. WIN55,212-2 did not change the EC50 value of 5-HT in stimulating current, but reduced the maximum effect. The CB1 receptor ligand [3H]-SR141716A and the CB1/CB2 receptor ligand [3H]-CP55940 did not specifically bind to parental HEK293 cells. In competition experiments on membranes of HEK293 cells transfected with the h5-HT3A receptor cDNA, WIN55,212-2, CP55940, anandamide and SR141716A did not affect [3H]-GR65630 binding, but 5-HT caused a concentration dependent-inhibition. In conclusion, cannabinoids stereoselectively inhibit currents through recombinant h5-HT3A receptors independently of cannabinoid receptors. Probably the cannabinoids act allosterically at a modulatory site of the h5-HT3A receptor. Thus the functional state of the receptor can be controlled by the endogenous ligand anandamide. This site is a potential target for new analgesic and antiemetic drugs.
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PMID:Direct inhibition by cannabinoids of human 5-HT3A receptors: probable involvement of an allosteric modulatory site. 1238 72

Using in situ hybridization histochemistry, a high degree of coexpression of the functional 5-HT3A subunit of the 5-HT3 receptor and the central CB1 cannabinoid receptor was detected in all subfields of the hippocampus and subgranular layer of the dentate gyrus (DG). Semi-quantitative analysis demonstrated that, depending on the hippocampal layer, 72-88% of CB1-expressing interneurons coexpress the 5-HT3A subunit. Within the DG, 5-HT3A/CB1 double-labeled neurons were confined to the subgranular layer, where close to 80% of all CB1-expressing basket neurons were found to contain 5-HT3A subunit transcripts. These results provide the first evidence indicating that the only ion channel receptor for serotonin and central CB1 cannabinoid receptor coexist in neurons containing the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). These findings suggest possible interactions between the cannabinoid and serotonergic systems at the level of GABA neurotransmission. However, activation of 5-HT3- or CB1-receptors are likely to have opposing regulatory effects on GABA neurotransmission, as 5-HT3 receptor activation by serotonin results in the release of GABA, while CB1 activation by cannabinoids results in inhibition of GABA release.
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PMID:Coexistence of serotonin 3 (5-HT3) and CB1 cannabinoid receptors in interneurons of hippocampus and dentate gyrus. 1254 27

Among all described serotonin (5-HT) receptors in mammals, the type three (5-HT3) is the only ligand-gated ion channel receptor for serotonin. By using double in situ hybridization histochemistry, we found co-expression of the functional 5-HT3A subunit of the 5-HT3 receptor and the central CB1 cannabinoid receptor in neurons of the rat telencephalon. Double-labeled 5-HT3A/CB1 neurons were found in the anterior olfactory nucleus, superficial and deep layers of the cortex, hippocampal formation (hippocampus, dentate gyrus, subiculum, and entorhinal cortex) and amygdala. Analysis of the proportion of neurons co-expressing 5-HT3A and CB1 receptors in the cortex and amygdala showed that, depending on the brain region, 37-53% of all neurons expressing the 5-HT3A subunit also expressed CB1 transcripts; 16-72% of the total population of neurons expressing CB1 mRNA co-expressed the 5-HT3A subunit. By using a combination of double in situ hybridization and immunohistochemistry, we demonstrated that 5-HT3A/CB1-expressing neurons contained the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). These results imply that in distinct regions of the telencephalon, GABA neurons that react to cannabinoids may also be responsive to serotonin through 5-HT3 receptors. Cellular coexistence of 5-HT3A and CB1 transcripts in interneurons of the cortex, hippocampal formation, and amygdala suggest possible interactions between the cannabinoid and serotonergic systems at the level of GABA neurotransmission in brain areas involved in cognition, memory, and emotion.
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PMID:Cannabinoid CB1 receptor and serotonin 3 receptor subunit A (5-HT3A) are co-expressed in GABA neurons in the rat telencephalon. 1464 80