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)

Ring-substituted psychoactive derivatives of amphetamine exhibited high affinities for a number of serotonin recognition sites. Derivatives of 2,5-DMA exhibited preferential high affinity at 5-HT2 serotonin receptors when compared to their relative affinities at 5-HT1 serotonin receptors. Furthermore, 2,5-DMA derivatives exhibited agonist-like binding characteristics at 5-HT2 serotonin receptors with the R(-) isomer being the more potent isomer. There were significant correlations between the in vitro affinities of 2,5-DMA derivatives at 5-HT2 serotonin receptors and their human hallucinogenic potencies as well as with their potencies in behavioral generalization studies, suggesting the importance of 5-HT2 serotonin receptors in mediating the hallucinogenic effects of the various 2,5-DMA derivatives. A pharmacological profile of the methylenedioxy-substituted amphetamine derivatives indicates that MDMA and MDA exhibited highest affinity for serotonin uptake sites, 5-HT2 serotonin, alpha 2-adrenergic and M-1 muscarinic receptors. The methylenedioxy amphetamine derivatives exhibited an inverse stereospecificity with respect to serotonin uptake sites versus postsynaptic 5-HT receptors with the S(+) isomer being more potent at the presynaptic recognition site, while the R(-) isomer was more potent at the postsynaptic recognition sites. Similar to the 2,5-DMA derivatives, MDMA and MDA exhibited agonist-like binding characteristics at 5-HT2 serotonin receptors. Unlike 2,5-DMA derivatives, MDMA and MDA demonstrated little selectivity for 5-HT2 versus 5-HT1 subtypes of receptors. The relatively weak hallucinogenic effects of the methylenedioxy-substituted amphetamine derivatives (when compared to the 2,5-DMA derivatives) may be mediated through actions at 5-HT2 serotonin receptors. In addition, the neurotoxic, psychotomimetic, analgesic, temperature regulation, and mood-altering effects of MDMA and other methylenedioxy-substituted derivatives may be mediated, in part, through their actions at other serotonin recognition sites in brain, including serotonin uptake sites and 5-HT1A serotonin receptors. Other behavioral, cardiovascular, and toxic effects of MDMA and related derivatives may be mediated by actions at other central and/or peripheral recognition sites, including muscarinic cholinergic receptors and alpha 2-adrenergic receptors, for which these compounds exhibit relatively high affinity. The precise mechanisms for the various effects of the amphetamine derivatives remain to be determined.
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PMID:Pharmacologic profile of amphetamine derivatives at various brain recognition sites: selective effects on serotonergic systems. 251 64

Most membrane receptors lose binding activity during purification and we studied the correlation between this event and differential solubilization of membrane lipids by detergents. Both 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate [Chaps; high critical micellar concentration (cmc) approximately 0.5%] and n-dodecyl beta-D-maltoside (DDM; low cmc approximately 0.009%) solubilized the 8-[3H]hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT)-binding serotonin 5-HT1A receptor (5-HT1A-R) optimally at 2% (w/v) detergent concentration despite the widely differing cmc of the two detergents. In contrast, n-octyl-beta-D-glucopyranoside (octyl glucoside; high cmc approximately 0.7%), Thesit (low cmc approximately 0.005%), and Triton X-100 (low cmc approximately 0.013%) solubilized virtually no [3H]8-OH-DPAT-binding activity. The total mass of solubilized lipids was always low at 0.5% detergent concentration and attained a plateau between 1 and 2.5% for all detergents except octyl glucoside. The mass of octyl glucoside-solubilized lipids showed an increasing trend even at 3.0% detergent concentration. The total amount of solubilized lipid is unrelated to the amount of 5-HT1A-R solubilized but the species of lipid is important. Thus Chaps and DDM, with diverse structures and cmc, both preferentially solubilized phospholipids enriched in saturated fatty acids (67 and 72%, respectively). In contrast, octyl glucoside, Triton X-100, and Thesit showed no preference in solubilizing phospholipids. Octyl glucoside, which solubilized significantly higher proportions of saturated fatty-acid-containing phosphatidylethanolamine (slightly higher saturated fatty acids in total phospholipids), also produced more (twofold higher) solubilized 5-HT1A sites than Triton X-100 and Thesit. This suggests an optimum involvement of saturated fatty acid side chains in forming tightly packed vesicles which stabilize the 5-HT1A-R more than the vesicles of higher fluidity formed by phospholipids containing higher proportions of cis-double-bonded unsaturated fatty acids. Indeed, delipidation of the 1.5% Chaps-solubilized receptor preparations by Sephacryl S-200 column chromatography eliminated essentially all [3H]8-OH-DPAT-binding activity. Therefore, for efficient recovery during solubilization and reconstitution of a prototypic heptahelical receptor (5-HT1A), it is essential to stabilize the receptor protein through association with saturated phospholipids.
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PMID:Differential solubilization of membrane lipids by detergents: coenrichment of the sheep brain serotonin 5-HT1A receptor with phospholipids containing predominantly saturated fatty acids. 834 57