Disease relevance of Htr1b

• BACKGROUND AND PURPOSE: This study examined the interaction between 5-hydroxytryptamine1B (5-HT1B) receptors and 20-hydroxyeiscosatetraenoic acid (20-HETE) in contributing to the acute fall in regional cerebral blood flow (rCBF) after subarachnoid hemorrhage (SAH) in rats [1].
• Overexpression of 5-HT1B receptor in dorsal raphe nucleus using Herpes Simplex Virus gene transfer increases anxiety behavior after inescapable stress [2].
• CONCLUSIONS: 5-HT1B, 5-HT2A/2B, and possibly 5-HT1D receptor subtypes likely play a role in posthypoxic myoclonus [3].
• The effects of classical and new anti-migraine drugs such as acetylsalicylic acid (ASA), sumatriptan and the new high efficacy 5-HT1B/1D agonist donitriptan (4-[4-[2-(2-aminoethyl)-1H-indol-5-yloxyl]acetyl]piperazinyl-1-yl]benzonitrile) were evaluated in comparison with the established model of neurogenic inflammation in the meninges [4].
• Involvement of 5-HT1A and 5-HT1B receptors for citalopram-induced hypothermia in the rat [5].

Psychiatry related information on Htr1b

• Our hypothesis was that presynaptic 5-hydroxytryptamine1B (5-HT1B) receptors, which inhibit the synthesis and release of serotonin in nerve terminals, may be increased in learned helplessness [6].
• But stimulation of hippocampal 5-HT1B receptors induced a selective change in the animal's emotional state, i.e., an initial decrease in locomotor activity and a neophobic reaction in response to a new object; such effects did not occur following stimulation of 5HT1A receptors [7].
• Direct infusion of 1 into the paraventricular nucleus of the hypothalamus of rats significantly inhibits food intake, implicating the role of 5-HT1B receptors in regulating feeding behavior in rodents [8].
• Second, 5-HT1B receptors are well characterized as controlling the activity of the serotonergic system, which is known to be involved in affective disorders and the mechanism of action of various antidepressants [9].
• If the effects mediated by 5HT1B receptors are endogenously active, their withdrawal during REM sleep may to some degree counterbalance the disfacilitation of XII motoneurons resulting from the withdrawal of their 5HT-mediated postsynaptic excitation [10].

High impact information on Htr1b

• Although this receptor is identical to rodent 5-HT1B receptors in binding to 5-HT, it differs profoundly in binding to many drugs [11].
• Here we show that replacement of a single amino acid in the human receptor (threonine at residue 355) with a corresponding asparagine found in rodent 5-HT1B receptors renders the pharmacology of the receptors essentially identical [11].
• Transient expression of this clone demonstrated high-affinity binding of [3H]5-HT with a pharmacological profile corresponding to that of the 5-HT1B subtype: 5-CT, 5-HT greater than propranolol greater than methysergide greater than rauwolscine greater than 8-OH-DPAT [12].
• Although the distribution of 5-HT-moduline binding sites was similar to that of 5-HT1B receptors, they did not overlap totally [13].
• Differences in distribution patterns were found in regions containing either high levels of 5-HT1B receptors such as globus pallidus and subiculum that were poorly labeled or in other regions such as dentate gyrus of hippocampus and cortex where the relative density of 5-HT-moduline binding sites was higher than that of 5-HT1B receptors [13].

Chemical compound and disease context of Htr1b

• 5-HT1B receptors: a novel target for lithium. Possible involvement in mood disorders [9].
• On the other hand, the 5-HT1A, 5-HT1B and beta adrenoceptor antagonists pindolol (2 mg/kg) and cyanopindolol (2 mg/kg), the 5-HT1A receptor agonist/antagonist ipsapirone (10 and 35 mg/kg) and haloperidol (0.25 and 0.5 mg/kg) showed a tendency towards enhancing the TFMPP- or m-CPP-induced hyperthermia [14].
• 1 Administration of the 5-HT1B receptor agonist m-chlorophenylpiperazine (m-CPP) to rats produces dose-dependent decreases in locomotor activity and food intake [15].
• 7 In conclusion, the 5-HT1B/D receptor agonists, rizatriptan and sumatriptan, elicit hypotension and bradycardia in the normotensive anaesthetized rat predominantly via activation of central 5-HT1A receptors, and a consequent reduction in sympathetic outflow [16].
• No hyperalgesia was seen after 5-HT1B, CGS-12066B maleate and m-trifluoromethylphenyl-piperazine hydrochloride; 5-HT2+IC, alpha methyl 5HT and (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl; or 5-HT3, 2-methyl-5-hydroxytryptamine maleate and phenylbiguanide, agonists [17].

Biological context of Htr1b

• Similarly, depletion of GRK-2 protein by stable transfection of full-length antisense OK-GRK2 cDNA blocked the desensitization of alpha2C-adrenergic receptors but not of 5-HT1B receptors [18].
• The present study investigates the comparative repopulation kinetics of 5-hydroxytryptamine (5-HT)1A, 5-HT1B, and 5-HT2A receptors in rat cortex homogenates after irreversible receptor inactivation by N-ethoxycarbonyl-1,2-ethoxydihydroquinoline [19].
• These findings suggest that agonist binding to 5-HT1A, 5-HT1B, and 5-HT1D sites is sensitive to NEM alkylation [20].
• The topographical distribution of these changes is consistent with up-regulation and/or increased production and transport of 5-HT1B and 5-HT2A receptors by the neostriatal projection neurons, as confirmed for the 5-HT2A receptor in a recent in situ hybridization study [21].
• Finally, the 5-HT1B receptor agonists that blocked synaptic transmission had no effect on resting membrane properties of raphe neurones [22].

Anatomical context of Htr1b

• The effects of long-term adrenalectomy on 5-HT1B receptors mRNA expression in cerebellum, striatum, frontal cortex and hippocampus of rats [23].
• This study was designed to assess the involvement of 5-HT1B receptors within the ventral tegmental area (VTA) in the regulation of mesolimbic dopaminergic transmission [24].
• 5-HT1B receptor mRNA levels in dorsal raphe nucleus: inverse association with anxiety behavior in the elevated plus maze [25].
• METHODS: The effects of intracisternal injection of 0.3 mL of arterial blood, artificial cerebrospinal fluid, and 5-HT on rCBF and the levels of 20-HETE and 5-HT in cerebrospinal fluid were measured in rats pretreated with vehicle, a 5-HT1B receptor antagonist (isamoltane hemifumarate), or an inhibitor of the synthesis of 20-HETE (HET0016) [1].
• The distribution of 5-HT1B and 5-HT1D receptors in all species examined so far, is very similar: high concentrations of sites are found in the nigro-striatal pathway, caudate-putamen, globus pallidus and especially substantia nigra [26].

Associations of Htr1b with chemical compounds

• The ability of the 5-HT1B receptor agonist anpirtoline and the selective 5-HT1B receptor antagonist NAS-181 to affect spatial learning in the water maze (WM) and aversive learning in the passive avoidance (PA) task were examined in the rat [27].
• Intra-tegmental infusion of CP 93129 (20, 40, and 80 microM), a 5-HT1B receptor agonist, increased extracellular DA concentrations in a concentration-dependent manner not only in the NACC but also in the VTA, indicating increased mesolimbic DA neuron activity [24].
• The increased DA neuron activity may be associated, at least in part, with the 5-HT1B receptor-mediated inhibition of VTA GABA release [24].
• CONCLUSIONS: These results suggest that the release of 5-HT after SAH activates 5-HT1B receptors and the synthesis of 20-HETE and that 20-HETE contributes to the acute fall in rCBF by potentiating the vasoconstrictor response of cerebral vessels to 5-HT [1].
• Rat 5-HT1B receptors recognize with high affinity a number of beta-adrenoceptor antagonists, such as SDZ 21-009, cyanopindolol, pindolol, propranolol and isamoltane [26].

Physical interactions of Htr1b

• The selective degeneration of serotoninergic neurons produced by an intracerebral injection of 5,7-dihydroxytryptamine was associated only with a significant loss of 5-HT1A binding to the dorsal raphe nucleus (-60%) and of 5-HT1B binding to the substantia nigra (-37%) [28].
• To characterize the specificity of endogenously expressed G protein-coupled receptor kinases (GRKs) for endogenous Gi-coupled alpha2C-adrenergic and serotonin 1B (5-HT1B) receptors in the opossum kidney (OK) cell line, we have isolated a 3.073-kb OK-GRK2 clone encoding a 689-amino acid protein that shares 94.2% amino acid identity with rat GRK2 [18].

Regulatory relationships of Htr1b

• 5-HT1B/1D receptor agonists stimulated binding in substantia nigra and in areas containing 5-HT1A receptors [29].
• The findings suggest that the NE neuronal system of the Locus coeruleus is stimulated by 5-HT1A and 5-HT1B receptor activation and inhibited by 5-HT2 receptors [30].
• The 5HT1B agonist RU24969 (2.5-5.0 mg/kg) and anpirtoline (2.0 mg/kg) induced a striking increase in striatal Fos-like immunoreactivity in rats [31].

Other interactions of Htr1b

• Co-infusion of the 5-HT1B receptor antagonist SB 216641 (10 microM), but not the 5-HT1A receptor antagonist WAY 100635 (10 microM) or the 5-HT1D/1A receptor antagonist BRL 15572 (10 microM), antagonized not only the effects of intra-tegmental CP 93129 (80 microM) on VTA DA and NAC DA but also on VTA GABA [24].
• NPY/PYY act via a different mechanism than presynaptic 5-HT1B receptors [32].
• 7. It is concluded that 5-HT application and stimulation of raphe obscurus increase the excitability of motoneurones by an action on a 5-HT1-like receptor which appears to be different from the 5-HT1A-and the 5-HT1B-binding sites characterized by others [33].
• Thus, serotonin can both depolarize and disinhibit SNr neurons via 5-HT2C and 5-HT1B receptors, respectively, but excitation may be limited by GABA released from axon collaterals [34].
• The present data also do not suggest the involvement of 5-HT3 mechanisms, but that D-16949 produces its discriminative stimulus effects in the rat primarily via agonistic actions at 5-HT1B receptors [35].

Analytical, diagnostic and therapeutic context of Htr1b

• Involvement of 5-HT1B receptors within the ventral tegmental area in regulation of mesolimbic dopaminergic neuronal activity via GABA mechanisms: a study with dual-probe microdialysis [24].
• In the present study, we combined receptor binding autoradiography with neurochemical ablation of 5-HT axons or electrolytic lesions of the dorsal thalamus in an effort to determine the neural elements upon which the 5-HT1B receptors were located [36].
• Despite the extensive reduction in serotonergic content, 5-HT1B mRNA did not change from control levels in any region when measured by in situ hybridization [37].
• In Experiment II, high dose MDMA had no effect on 5-HT1B mRNA in any brain region either 1 or 14 days after treatment [37].
• The local perfusion (30-300 microM) of the selective 5-HT1B receptor agonist CP-93,129 to freely moving rats decreased 5-HT release in the DR and more markedly in the MnR [38].

References