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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Modulation of the hyperpolarization-activated cation current, Ih, by noradrenaline (NA) and serotonin (5-HT) was examined in guinea-pig and cat medial and lateral geniculate relay neurones using the in vitro slice technique. 2. In the absence of pharmacological antagonists, local application of NA resulted in a slow depolarization and decrease in apparent input conductance, a response which was blocked by local or bath application of the alpha 1-adrenoceptor antagonist prazosin. Application of NA after pharmacological block of alpha 1- and alpha 2-adrenoceptors, or application of 5-HT in all conditions, induced a 1-3 mV slow depolarization which was associated with a pronounced increase in apparent input conductance. This response to NA and 5-HT persisted during blocked synaptic transmission and was present in both the guinea-pig and cat medial and lateral geniculate nuclei. 3. The increase in membrane conductance elicited by NA was mimicked by the beta-specific agonist isoprenaline and blocked by the beta-antagonists propranolol and atenolol, indicating that it is mediated by beta-adrenoceptors. The response to 5-HT was blocked by the 5-HT1 and 5-HT2 antagonist methysergide, but not by the 5-HT2 antagonist ritanserin. Applications of either the 5-HT1A agonist ipsapirone or the partial agonist 8-hydroxy-dipropylaminotetralin (8-OHDPAT) were without effect. 4. Current versus voltage relationships obtained under voltage clamp revealed NA and 5-HT to cause a voltage-dependent inward shift at membrane potentials negative to approximately -60 mV. This response appeared to be shared by NA and 5-HT since maximal application of 5-HT greatly reduced or abolished the response to NA. 5. Application of NA and/or 5-HT during hyperpolarizing voltage steps in voltage clamp resulted in a marked increase in amplitude of the hyperpolarization-activated cation current, Ih. In addition, the rate of activation of Ih was strongly increased during activation of beta-adrenoceptors. 6. The activation curve of the conductance underlying Ih (Gh) was shifted by 4-6 mV on the voltage axis with NA and/or 5-HT. The positive shift of Gh activation in the voltage domain resulted in an increase in the amplitude of Gh which is active at resting, and more hyperpolarized, membrane potentials. The subsequent increase in resting membrane conductance decreased the responsiveness of thalamic neurones to hyperpolarizations of all durations. 7. Local or bath application of caesium blocked both Ih and the increase in membrane conductance in response to NA and 5-HT. By contrast, barium blocked neither Ih nor the responses to NA and 5-HT.(ABSTRACT TRUNCATED AT 400 WORDS)
J Physiol 1990 Dec
PMID:Noradrenergic and serotonergic modulation of a hyperpolarization-activated cation current in thalamic relay neurones. 171 44

Only 25 years ago, tobacco dependence was believed to be a simple overuse problem. Research in the last 5 years has demonstrated a much more complex and profound neurochemical and behavioral disorder. Nicotine receptors in the locus coeruleus and the midbrain mesolimbic dopaminergic system activate both arousal state and enhance cognitive functioning (locus coeruleus) and activate the brain's "pleasure center" (mesolimbic system). Pharmacologic treatments, which must be completely integrated into the behavioral treatment plan, alter these profound central nervous system nicotine effects. Currently the only agent with clear scientific evidence for treatment efficacy is nicotine itself. Available only in a transmucosally delivered ion-exchange resin as nicotine polacrilex (Nicorette), nicotine should soon be available in other delivery forms that will have different absorption kinetics: transdermal patch, nasal spray, and vapor inhaler. Other agents in various phases of preclinical and clinical evaluation include 5-HT1A partial agonists such as buspirone; alpha 2-noradrenergic agonists such as clonidine; tricyclics such as doxepin; serotonin re-uptake antagonists such as fluoxetine; ACTH; 5-HT2 antagonists such as ritanserin; central excitatory amino acid inhibitors such as kynurenate; and calcium channel blockers.
Clin Chest Med 1991 Dec
PMID:Pharmacologic approaches to smoking cessation. 174 93

The serotonergic neurons of the mammalian brain comprise one of the most expansive chemical systems known. The cell bodies are largely confined to the midline (raphe) region of the brain stem in two general clusters: a superior group that consists of the dorsal raphe nucleus (B-7 and B-6), median raphe nucleus (B-8 and B-5), caudal linear nucleus (rostral B-8), and supralemniscal nucleus (B-9), and an inferior group that consists of nucleus raphe obscurus (B-2), nucleus raphe pallidus (B-1), nucleus raphe magnus (B-3), ventral lateral medulla (B-1/B-3), and the area postrema. The axons from these cells project throughout the neuroaxis from the spinal cord to the olfactory bulb and from the cerebral cortex to the hypothalamus. The development of this giant system begins very early in gestation and is influenced by a variety of growth regulatory factors, including the astroglial protein S-100 beta. Evidence will be presented that the serotonergic system plays a major role in the maturation of the brain by interacting with the 5-HT1A receptors which are most dense during these early developmental periods. The 5-HT1A receptor is located on both neurons and astrocytes, and in the latter cells may serve to stimulate release of S-100 beta. The developmental role of 5-HT appears to become dormant as the brain matures, and during aging and Alzheimer's disease, 5-HT receptors are significantly depressed. However, specific damage to 5-HT fibers in the adult brain by 5,7-dihydroxytryptamine produces a sharp fall in the levels of 5-HT which seems to reactivate the developmental signals in the brain. Not only are the serotonergic fibers encouraged to sprout and expand their territory, but the stimulation of the astrocytic growth factor by a 5-HT1A agonist is reinstated. The ability to recall developmental processes in the adult brain by interrupting the 5-HT fibers may provide important tools for understanding and treating the aged brain.
J Clin Psychiatry 1991 Dec
PMID:Awakening the sleeping giant: anatomy and plasticity of the brain serotonergic system. 175 58

RDC4 is a guanine nucleotide-binding protein-coupled receptor clone originally isolated from a canine thyroid cDNA library by Libert and colleagues [Science (Washington D. C.) 244:569-572 (1989)]. We have isolated the corresponding genomic clone for RDC4, have expressed this clone in murine LM (tk-) fibroblasts, and have determined that it encodes a serotonin 5-hydroxytryptamine1D (5-HT1D) receptor. RDC4 is an intronless gene encoding a protein of 377 amino acids, which exhibits greatest sequence identity (43%) to the 5-HT1A receptor and lower overall homology to other serotonergic and catecholaminergic receptors. Membranes prepared from murine LM (tk-) fibroblasts stably transfected with this clone were shown to bind [3H]5-HT in a saturable manner and displayed an apparently homogeneous population of high affinity (Kd = 3.6 nM, Bmax = 275 fmol/mg of protein) [3H]5-HT binding sites. High affinity [3H] 5-HT binding was unchanged using assay conditions [1 microM (+/- )-pindolol and 1 microM (R)-(+/- )-SCH 23390) to pharmacologically mask 5-HT1A, 5-HT1B, and 5-HT1C receptors. Serotonergic ligands displaced specific [3H]5-HT binding with a rank order of potency expected of a 5-HT1D receptor subtype, 5-carboxyamidotryptamine greater than 5-HT greater than yohimbine greater than 8-hydroxy-2-(di-n-propylamino)tetralin greater than ketanserin = spiperone greater than zacopride. Further, transfected cells responded to addition of 5-HT by decreasing the level of forskolin-stimulated cAMP accumulation. These data indicate that the gene RDC4 encodes a functional 5-HT1D receptor.
Mol Pharmacol 1991 Dec
PMID:Expression and pharmacological characterization of a canine 5-hydroxytryptamine1D receptor subtype. 175 39

The tricyclic antidepressant imipramine was established as a discriminative stimulus in pigeons at two doses (3.0 or 5.6 mg/kg). Because imipramine has multiple effects on different neurotransmitter systems, a range of compounds from several pharmacological classes were tested for substitution. The tricyclic antidepressants desipramine, amitriptyline and doxepin, all of which block serotonin (5-HT) and norepinephrine (NE) reuptake, resulted in imipramine-key responding. The psychomotor stimulants cocaine and d-amphetamine also occasioned responding on the imipramine key, as did the NE reuptake inhibitor tomoxetine; nomifensine, which blocks the reuptake of both NE and dopamine (DA), also resulted in responding on the key correlated with imipramine injections. Bupropion, a DA reuptake inhibitor, resulted in drug key responding but substitution did not occur with another DA uptake inhibitor GBR 12909. The alpha-2 agonist clonidine, the 5-HT2 antagonist ritanserin or the 5-HT reuptake inhibitor fluoxetine also did not occasion drug-key responding. Drug-appropriate responding occurred in pigeons trained at the lower dose of imipramine with the 5-HT1A compounds 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide and gepirone; partial substitution occurred in pigeons trained with the higher dose of imipramine. Substitution for the imipramine stimulus by gepirone, an antidepressant with actions mediated by the 5-HT1A receptor, as well as with 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide, suggests that imipramine may have effects at this receptor site and confirms reports that compounds active at this receptor may have antidepressant activity. This appears to be the first report of the successful, long-term establishment of imipramine as a discriminative stimulus without the development of toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
J Pharmacol Exp Ther 1991 Dec
PMID:Imipramine as a discriminative stimulus. 176 63

The affinity of a new serotonin (S) derivative, serotonin-O-carboxymethyl-glycyl-tyrosinamide (S-CM-GTNH2), for the various 5-hydroxytryptamine (5-HT)1 receptor subtypes was tested using quantitative autoradiography on rat and guinea pig brain sections. In the rat, S-CM-GTNH2 is 57 and 24 times more potent at 5-HT1B sites (IC50 = 28 nM) than at 5-HT1A (IC50 = 1600 nM) and 5-HT1C sites (IC50 = 670 nM), respectively. In the guinea pig, the affinity of S-CM-GTNH2 for 5-HT1D sites (IC50 = 67 nM) is 21 times higher than at 5-HT1A sites (IC50 = 1400 nM). S-CM-GTNH2 shows a low affinity (less than 10 microM) for 5-HT2 and 5-HT3 binding sites. This new ligand is therefore highly specific for 5-HT1B and 5-HT1D binding sites and can be used to further characterize the involvement of these subtypes in physiological studies focusing particularly on behavioral effects.
J Pharmacol Exp Ther 1991 Dec
PMID:Pharmacological characterization of serotonin-O-carboxymethyl-glycyl-tyrosinamide, a new selective indolic ligand for 5-hydroxytryptamine (5-HT)1B and 5-HT1D binding sites. 176 84

Lisuride is an ergot derivative with central dopaminergic (D2 agonistic) and serotonergic (5-HT1A agonistic) activity. The effect of lisuride on experimental cerebral infarction in rats was investigated. Cerebral infarction was induced by intracarotid infusion of a 50-microliters mixture in which deformed and rigid red blood cells treated with hypertonic solution were contained. Lisuride or 0.9% NaCl was administered subcutaneously 30 min before induction of cerebral infarction. Lisuride (0.01 mg/kg) not only prolonged the survival time of the animals but also suppressed cerebral edema, increase in the electrolytes content and histological damage in the brain. These results suggest that lisuride has a protective effect against cerebral infarction.
Nihon Yakurigaku Zasshi 1991 Dec
PMID:[Effect of lisuride on experimental cerebral infarction in rats]. 178 26

Previous works have indicated that insulin stress activates the serotonin (5-HT) and sympathoadrenal systems in the fasted rat. In addition, recent studies have shown that activation of either the 5-HT1A, the 5-HT1C or the 5-HT2 receptor triggers adrenal catecholamine release. Then, the aim of this study was to investigate whether brain 5-HT, by means of these receptors, mediates insulin-induced adrenal catecholamine release. For that purpose, both plasma epinephrine (Epi), norepinephrine (NE) and glucose levels were measured in conscious rats bearing intracardiac catheters. The intravenous administration of insulin (1 IU/kg) triggered hypoglycemia throughout the following 120 min in both fed and overnight fasted rats. Insulin stress elicited within 30 min a 5- and 38-fold increase in plasma Epi levels in fed and fasted rats, respectively. This change was associated with significant elevations in plasma NE levels in the fasted rats only. The intravenous administration of the mixed 5-HT1A receptor/beta-adrenoceptor blocker (-)-propranolol (5 mg/kg) to fasted rats did not modify plasma glucose and catecholamine peak responses to insulin; however, at later times, insulin triggered hypoglycemic convulsions in (-)-propranolol- but not in saline-pretreated rats. Besides, pretreatments with the 5-HT1C/5-HT2 receptor blocker LY 53857 (0.5 mg/kg), or the 5-HT1/5-HT2 receptor antagonist metergoline (3 mg/kg), did not diminish plasma catecholamine responses to insulin stress. Similarly, none of these antagonists affected plasma glucose recovery. These results seem to indicate that the sympathoadrenal response to insulin administration is not mediated by 5-HT.
Neuroendocrinology 1991 Dec
PMID:Influence of 5-HT1 and 5-HT2 receptor antagonists on insulin-induced adrenomedullary catecholamine release. 178 47

The effects of chronic administration of lithium, short-term administration of lithium, chronic administration of DMI and a combination of short-term administration of lithium and chronic administration of DMI on second messenger responses were studied in the hippocampus of the rat. Lithium reduced the ability of carbachol to inhibit forskolin-stimulated activity of adenylate cyclase in hippocampal membranes but had no effect on carbachol-stimulated formation of inositol phosphate in hippocampal slices. Lithium, however, reduced the degree of stimulation of formation of inositol phosphate, induced by noradrenaline. Desimipramine alone did not affect carbachol- or noradrenaline-mediated reactions and a combination of short-term administration of lithium and chronic administration of DMI did not potentiate the action of lithium on adenylate cyclase. Both lithium and DMI abolished the inhibition by 5-HT of carbachol-stimulated formation of inositol phosphate a 5-HT1A receptor-mediated response. It is concluded that the chronic effects of administration of lithium may be related to actions at the G protein level and that different modes of coupling of receptors to G proteins may be responsible for the variety of effects observed.
Neuropharmacology 1991 Dec
PMID:Effects of lithium and desimipramine on second messenger responses in rat hippocampus: relation to G protein effects. 178 83

Intrathecal administration (ith) of 5-hydroxytryptamine (5-HT, 1.56, 3.125, 6.25 and 12.5 micrograms/10 microliters) to conscious rats produced a marked dose-dependent hypertensive effect without significant change in heart rate (HR). Ith administration of fluoxetine (10 micrograms/microliters), one of the presynaptic reuptake inhibitors of 5-HT, produced a marked increase in the mean arterial blood pressure (mABP). This effect could be prevented by a pretreatment with cinanserin (25 micrograms ith) as a blocker of 5-HT receptor. It was further observed that ith of 8-OH-DAPT (2.5, 5, 10 micrograms/10 microliters), a 5-HT1A receptor agonist, produced a dose-dependent increase of mABP and lowering of HR. However, ith of 5-HT3 receptor agonist 2-Methylserotonin (25, 50, 100 micrograms/10 microliters), decreased mABP markedly without change in HR. The results indicate that 5-HT in the spinal cord may extra hypertensive effect via 5-HT1A receptor and a hypotensive effect via 5-HT3 receptor. This gives a possible explanation about the conflicting reports concerning the effect of 5-HT in the central nervous system on blood pressure.
Sheng Li Xue Bao 1991 Dec
PMID:[Cardiovascular reactions mediated by 5-HT1A and 5-HT3 receptors in the spinal cord of conscious rats]. 179 18


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