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 characteristics of high affinity [3H]5-HT (5-hydroxytryptamine) binding to non 5-HT1A non 5-HT1C sites were examined in crude membranes prepared from different regions of guinea-pig and pigeon brains. The coupling of these sites to adenylate cyclase was examined, and its pharmacological profile investigated. In the presence of 100 nmol/l 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) and 100 nmol/l mesulergine, [3H]5-HT labelled with nanomolar affinity an apparently homogeneous population of recognition sites in guinea-pig and pigeon brain membranes. The rank order of affinities of agonists and antagonists (5-CT (5-carboxamidotryptamine) greater than 5-HT greater than RU 24969 (5-methoxy-3-(1,2,3,6-tetrahydro-4- pyridinyl)-1H indole succinate) greater than yohimbine greater than or equal to rauwolscine greater than DP-5-CT (N,N dipropyl-5-carboxamidotryptamine) greater than or equal to mianserin greater than 8-OH-DPAT greater than mesulergine greater than SDZ 21-009 ((+/-)-4(3-tert-butyl-amino-2-hydroxypropoxy)-indol-2 carbonic acid isopropyl ester) greater than (-)propranolol), as well as their individual pKD values, were very similar to those at porcine caudate 5-HT1D sites and clearly different from those at rat cortex 5-HT1B sites. In the substantia nigra of the guinea-pig the 5-HT receptor-mediated inhibition of forskolin-stimulated adenylate cyclase had a pharmacological profile fully comparable to that of 5-HT1D binding sites (5-CT greater than 5-HT greater than yohimbine greater than RU 24969 greater than 8-OH-DPAT greater than SDZ 21-009 = isamoltane greater than (-)pindolol greater than (-)propranolol).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:5-HT1D receptors in guinea-pig and pigeon brain. Radioligand binding and biochemical studies. 253 24

The regional distribution of high affinity [3H]5-HT recognition sites in the brain of several vertebrates (pigeon, rat, mouse, guinea-pig, cat, dog, monkey and human) was analyzed using in vitro autoradiography. The presence of subtypes of 5-HT1 binding sites was investigated by selective displacements with 8-OH-DPAT, mesulergine and (+/-)SDZ 21-009 at appropriate concentrations to block 5-HT1A, 5-HT1C and 5-HT1B sites respectively. In addition, 5-HT1A and 5-HT1C sites were directly visualized with the more selective radioligands [3H]8-OH-DPAT and [3H]mesulergine, respectively. In the pigeon brain, total [3H]5-HT binding sites were enriched in all telencephalic areas. Densely labelled regions were also present in the optic tectum and the brainstem. No binding was observed in the cerebellum. 8-OH-DPAT and mesulergine only displaced a small proportion of [3H]5-HT binding in most of the areas where high concentrations of 5-HT1 sites were found. (+/-)SDZ 21-009 did not affect [3H]5-HT binding in the regions examined. Taking into account our pharmacological studies, these results suggest that the majority of 5-HT1 sites belong to the 5-HT1D subtype in the pigeon brain. In the mammalian species investigated high levels of [3H]5-HT binding were found in the neo-cortex, hippocampal formation, basal ganglia and related structures (substantia nigra), raphe dorsalis, nucleus superior colliculus and choroid plexus. However, these brain areas were differentially enriched in subtypes of 5-HT1 recognition sites.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:5.HT1 receptors in the vertebrate brain. Regional distribution examined by autoradiography. 253 25

[3H]Rauwolscine binds with high affinity to alpha 2-adrenoceptors (Kd = 4.8 +/- 1.3 nM, Bmax = 79 +/- 26 fmol/mg protein, micromolar affinity for 5-HT) as well as to 5-HT1-like receptors (Kd = 13 +/- 2.7 nM, Bmax = 147 +/- 11.4 fmol/mg protein, nanomolar affinity for 5-HT) in human brain cortex membranes. The Ki values of 11 serotonergic compounds for the latter receptors agreed closely with those previously reported for 5-HT1A sites but not with those for 5-HT1B, 5-HT1C and 5-HT1D sites.
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PMID:[3H]rauwolscine labels alpha 2-adrenoceptors and 5-HT1A receptors in human cerebral cortex. 253 40

The binding affinities of four hallucinogenic agents were analyzed at nine neurotransmitter binding sites in human cortex. d-Lysergic acid diethylamide (d-LSD), N,N-dimethyltryptamine (DMT), 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB) display highest affinity for the recently identified "DOB binding site" labeled by 77Br-R(-)DOB. The phenalkylamines, DOI and DOB, display subnanomolar affinity for the 77Br-R(-)DOB-labeled site, whereas the indolealkylamines, d-LSD and DMT, display nanomolar affinity for this site. d-LSD was the most potent of the four hallucinogens at six of the other eight sites analyzed in this study. All four hallucinogens also display high affinity for the 5-hydroxytryptamine2 (5-HT2) receptor subtype, with potencies ranging from 4 to 360 nM. Marked differences in relative affinities were observed between the indolealkylamines and the phenalkylamines at the 5-HT1A, 5-HT1D, and DOB binding sites. These rank-order differences in affinities are likely to account for the differing effects of these agents in various biochemical and physiological assays.
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PMID:Hallucinogenic drug interactions with neurotransmitter receptor binding sites in human cortex. 254 May 5

We have previously reported the presence of a 5-HT1 (serotonin)-like receptor coupled in an inhibitory manner to adenylate cyclase in the opossum kidney cell line, which is derived from the kidney of a North American opossum. Pharmacological data from binding and cyclic AMP production studies indicate that this receptor does not have characteristics of a 5-HT1A, 5-HT1C or 5-HT1D receptor, but is similar to 5-HT1B receptors found in rodent tissues. Many serotonergic drugs, including 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyrindinyl)1H-indol, 5-HT and methysergide, but not (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide or buspirone, were full agonists at this receptor as defined by the inhibition of bovine parathyroid hormone peptide fragment 1-34-stimulated cyclic AMP production in an intact cell assay. Several classical beta adrenergic antagonists including propranolol and cyanopindolol were also full agonists at this receptor. Radioligand binding studies using [125I](-)-iodocyanopindolol gave a Bmax of 88 fmol/mg of protein and a KD of 47 pM for saturation experiments carried out in the presence of GTP. In the absence of GTP, the binding data were significantly better fit by a two-site model with KD values of 10 and 345 pM. Inhibition binding experiments were consistent with the results of the cyclic AMP experiments. The identification of 5-HT1B receptors in a tissue derived from the opossum kidney suggests that these receptors may be distributed more widely than previously thought, inasmuch as other studies have found them only in neuronal tissues of rodents.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of serotonin-1B receptors negatively coupled to adenylate cyclase in OK cells, a renal epithelial cell line from the opossum. 254 34

The ability of sumatriptan (GR 43175; 3-[2-dimethylamino]ethyl-N-methyl-1H-indole-5 methane sulphonamide) to interact with 13 neurotransmitter receptor sites was determined using radioligand binding techniques. Sumatriptan displayed the highest affinity for 5-HT1D (Ki = 17 nM) and 5-HT1B (Ki = 27 nM) binding sites and was slightly less potent at 5-HT1A binding sites (Ki = 100 nM). By contrast, sumatriptan was essentially inactive (Ki greater than 10,000 nM) at each of the 10 other binding sites analyzed. These data indicate that sumatriptan interacts selectively with 5-HT1B and 5-HT1D sites and suggest that these interactions may be the basis of its apparent efficacy in the acute treatment of migraine.
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PMID:Sumatriptan (GR 43175) interacts selectively with 5-HT1B and 5-HT1D binding sites. 254 59

GR 43175 (3-[2-dimethylamino]ethyl-N-methyl-1 H-indole-5 methane sulphonamide) is a novel 5-HT1-like receptor-selective agonist which was reported to be active in the treatment of migraine attacks. The effects of the compound were investigated in radioligand binding studies and in functional models for 5-HT1A, 5-HT1B, and 5-HT1D receptors (inhibition of forskolin-stimulated adenylate cyclase activity in calf hippocampus, rat and calf substantia nigra, respectively) and 5-HT1C receptors (stimulation of inositol phosphate production in pig choroid plexus). GR 43175 displayed the following order of affinity for 5-HT recognition sites (pKD values, -log mol/l, in parentheses): 5-HT1D (7.54) greater than 5-HT1B (6.35) greater than 5-HT1A (6.13) much greater than 5-HT1C (4.13) greater than 5-HT2 (3.67). The same order of potency was observed at functional 5-HT1 receptors, at which GR 43175 acted as a full agonist, with the exception of the 5-HT1C receptor, where the compound was a weak antagonist (pEC50 or pKB values, -log mol/l, in parentheses): 5-HT1D (6.28) greater than 5-HT1B (6.03) greater than 5-HT1A (5.57) much greater than 5-HT1C (4.25). The present data show that GR 43175 interacts preferentially as an agonist with 5-HT1B and 5-HT1D receptors. Since 5-HT1B receptors have not yet been identified in human brain, it seems possible that it is the 5-HT1D receptor which is relevant to the reported antimigraine effects of this compound.
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PMID:How selective is GR 43175? Interactions with functional 5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D receptors. 255 30

The existence of two different functional receptors for 5-hydroxytryptamine (5-HT) was first proposed by Gaddum and Picarelli. Aided by the development of radioligand binding techniques, the heterogeneity of 5-HT receptors has become more apparent in the past ten years. There are three main types of 5-HT receptors: 5-HT1, 5-HT2 and 5-HT3. Moreover, 5-HT1 is heterogenous and can be divided into 5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D subtypes. 5-HT1B is probably related to the 5-HT autoreceptor controlling 5-HT release. Multiple 5-HT receptors are differentially distributed throughout the brain, and the agonist-receptor interaction is altered by physical parameters and chemicals, suggesting that the receptors may be physiologically relevant. Three 5-HT receptor subtypes, 5-HT1A, 5-HT1C and 5-HT2, have been cloned. All three receptors contain approximately 450 amino acids arrayed as seven transmembrane domains. 5-HT1 and 5-HT1A are coupled to adenylate cyclase positively and negatively, respectively, while 5-HT1C and 5-HT2 are coupled positively to phospholipase C. 5-HT1A is also coupled to the opening of K+ channels in hippocampal pyramidal cells. A number of 5-HT-induced physiological responses have been shown to correlate with the 5-HT receptor subtypes. Based on a number of pharmacological studies, it seems likely that the mode of action of certain psychotropic drugs is closely related to the activity of central 5-HT receptors.
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PMID:[5-Hydroxytryptamine receptors]. 255 57

In examining anxiety and the response of animal models to serotonergic drugs, four aspects should be taken into account: (1) the serotonin receptor is subdivided into at least six receptor subtypes; (2) benzodiazepines have acute anxiety-relieving effects, whereas antidepressants, serotonin-uptake inhibitors, buspirone, and serotonin antagonists have antianxiety effects only after prolonged administration; (3) diagnostic criteria differentiate several distinguishable anxiety disorders that have different responsiveness to serotonin-related drugs, and (4) various types of animal models exist, each responding differently to serotonin-related drugs. Perhaps particular animal models are relevant only for the study of one particular type of anxiety disorder. This differentiated view will be used when discussing the role of 5-hydroxytryptamine (5-HT) receptor subtypes in anxiety disorders and anxiety models. The 5-HT1A receptor is implicated in anxiety by the compounds buspirone and 8-hydroxy-2-(di-n-propyl-aminotetraline) (OHDPAT). The 5-HT1B or the 5-HT1D receptors play a role in the 'defensive burying' anxiety model and probably mediate antidepressant and antianxiety effects of serotonin-uptake inhibitors. The 5-HT1C receptor plays a role in the aversive brain stimulation anxiety model and could play a role in antianxiety effects of mianserin. The 5-HT2 receptor is selectively blocked by ritanserin. In animal 'conflict models' for anxiety, 5-HT-2-receptor antagonists are active, although they are weaker than the benzodiazepines. The 5-HT3-receptor antagonists are reported to be active in social interaction models for anxiety; however, clinical experience in anxiety using these compounds is not yet available.
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PMID:Animal models for anxiety and response to serotonergic drugs. 256 38

1. The effect of serotonin on chloride secretion in hen colon was studied under short circuit conditions. 2. Serotonin added to the serosal side induced a short-lived peak increase in Cl(-)-secretion (6.2 +/- 1.0 mumole.cm-2.h-1), in short circuit current (5.4 +/- 0.7 mumole.cm-2.h-1) and in cord conductance (8.1 +/- 0.7 mS.cm-2) with an apparent EC50 around 8 microM, and a more prolonged rise in chloride secretion of around 3.0 mumole.cm-2.h-1. 3. The short circuit current is a reasonable measure of net chloride secretion at the peak. 4. Several specific and non-specific serotonin receptor antagonists were studied for their influence on the serotonin induced peak response in short circuit current and cord conductance. 5. These antagonists covered the whole range of currently defined serotonin receptor types and subtypes: 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT2, and 5-HT3. 6. Adrenergic, cholinergic and histaminergic receptor antagonists were also tested for an interaction at the serotonin receptor involved in Ca(-)-secretion. 7. None of the antagonists had any influence on the serotonin response in short circuit current or cord conductance.
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PMID:Serotonin receptors for chloride secretion in hen colon. 257 32


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