Disease relevance of HTR7

• At this stage in the migraine process, activation of specific subtypes of 5-HT1 receptors has proven clinically effective in relieving migraine pain [1].
• Blocking 5-HT1A receptors attenuated bradycardias evoked by stimulating baroreceptor and cardiopulmonary afferents but not arterial chemoreceptors, whereas antagonizing 5-HT7 receptors markedly attenuated all these reflex bradycardias [2].
• Serotonin via 5-HT7 receptors activates p38 mitogen-activated protein kinase and protein kinase C epsilon resulting in interleukin-6 synthesis in human U373 MG astrocytoma cells [3].
• To this end, pulmonary ventilation (V(E)) of rats was measured before and after intra-AVPO microinjection of methysergide (a 5-HT1 and 5-HT2 receptor antagonist), WAY-100635 (a 5-HT1A receptor antagonist) and SB-269970 (a 5-HT7 receptor antagonist), followed by 60 min of hypoxia exposure (7% O2) [4].
• Recently, we have demonstrated that potassium channels containing G-protein-activated potassium channel 2 (GIRK2) subunits play a significant role in hypothermia induced by several neurotransmitter receptor agonists, including the serotonin (5-HT)1A/5-HT7 receptor agonist 8-OH-DPAT [R-(+)-8-hydroxy-2-(di-n-propylamino) tetralin] [5].

Psychiatry related information on HTR7

• Assignment of the 5HT7 receptor gene (HTR7) to chromosome 10q and exclusion of genetic linkage with Tourette syndrome [6].
• Allele-specific PCR was used to genotype the HTR7 marker in 53 trios consisting of subjects with autistic disorder and both parents [7].
• The human serotonin 7 (5-HT7) receptor gene: genomic organization and systematic mutation screening in schizophrenia and bipolar affective disorder [8].
• Phase-shifting effect of 8-OH-DPAT, a 5-HT1A/5-HT7 receptor agonist, on locomotor activity in golden hamster in constant darkness [9].
• The 5-HT7-/- mice spent less time in and had less frequent episodes of REM sleep, also consistent with an antidepressantlike state [10].

High impact information on HTR7

• A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of mammalian circadian rhythms [11].
• 5-HT7 mRNA is expressed discretely throughout the CNS, predominantly in the thalamus and hypothalamus [11].
• Indeed, 5-HT7 receptors have been implicated in the pathophysiology of several disorders; they play a role in smooth muscle relaxation within the vasculature and in the gastrointestinal tract [12].
• In doing so, they advocate that the so-called '5-HT1-like' receptors, having been shown to be a heterogeneous population of 5-HT1B, 5-HT1D and 5-HT7 receptors, are now redundant [13].
• In recent years, cloning has revealed the existence of no less than 14 mammalian 5-HT receptors, as well as evidence that isoforms of the 5-HT4 and 5-HT7 receptors are generated by alternative splicing [14].

Chemical compound and disease context of HTR7

• Physical mapping of the serotonin 5-HT(7) receptor gene (HTR7) to chromosome 10 and pseudogene (HTR7P) to chromosome 12, and testing of linkage disequilibrium between HTR7 and autistic disorder [7].

Biological context of HTR7

• First, we made a tentative assignment to chromosome 10, based on hybridization of an HTR7 probe to a Southern blot of DNA from somatic cell hybrids [6].
• With respect to the pro279leu HTR7 polymorphism, one Caucasian male responder to clozapine was observed to be heterozygous (pro/leu 279 genotype) [15].
• We then identified a genetic polymorphism at the HTR7 locus [6].
• After determining over 3 kb of previously unpublished sequence from introns 1 and 2 of HTR7, a single base (C/T) polymorphism in the second intron of HTR7 was found [7].
• This study examined the hypothesis that genetic variation in 5-HT1A, 5-HT6, and 5-HT7 receptor genes is involved in the variability observed in response to clozapine [15].

Anatomical context of HTR7

• 5HT7 receptor mRNA was enriched in the ciliary body, choroid, conjunctiva, and iris, with much lower levels in the retina and ciliary epithelium [16].
• Optic nerve tissue of 1-2 donors exhibited the presence of 5HT2B, 5HT5, and 5HT7 receptor mRNAs [16].
• In HeLa cells expressing the 5HT7 receptor subtype, oleamide caused a concentration-dependent increase in cAMP accumulation but with lower efficacy than that observed by 5HT [17].
• 5-HT7 mRNA is most abundant in the hippocampus, neocortex, and hypothalamus [18].
• In contrast, messages for all 5-HT receptors tested were detected in human brain astrocytes with a predominance of the 5-HT2A and 5-HT7 subtypes [19].

Associations of HTR7 with chemical compounds

• A novel serotonin receptor designated 5HT7 (genetic locus HTR7) was cloned in 1993 [6].
• Evaluation of serotonin (5HT), melatonin (MT), and melatonin-related receptors (MRR) showed expression of the isoforms 5HT2B, 5HT7, and MT1 genes in almost all the tested samples [20].
• This study investigated the effects of the T-->C 267 polymorphism in the 5HT6 receptor gene and two rare Pro279Leu and Thr92Lys substitutions in the 5HT7 receptor gene on risperidone efficacy after rigorous control for nongenetic confounders [21].
• Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase [22].
• In contrast, 5-carboxamidotryptamine induced strong increases (> or = 400%, P < .005) in basal cyclic AMP levels that were abolished by mesulergine, a nonselective 5-HT7 receptor antagonist [19].

Regulatory relationships of HTR7

• Furthermore, IL-6 synthesis was induced by the 5-HT7 receptor agonist carboxamidotryptamin [3].
• Clozapine downregulates 5-hydroxytryptamine6 (5-HT6) and upregulates 5-HT7 receptors in HeLa cells [23].

Other interactions of HTR7

• Risperidone (a widely used atypical antipsychotic agent) and several other atypicals have high affinities for 5-HT6 and 5-HT7 receptors [21].
• RS-64459 and the enantiomers of RS-30199 had weaker affinity for 5-HT2C and 5-HT7 receptors [24].
• In addition, association was tested using single nucleotide polymorphisms (SNPs) within the KCNMA1, HTR7 and SLC18A2 genes that may relate to a finding on chromosome 10 [25].
• Isolated microvessels and capillaries consistently expressed messages for the h5-HT1B, h5-HT1D, 5-HT1F, 5-HT2A but not 5-HT7 receptors [19].
• In this report, we show that the 5-HT-induced IL-6 release is mediated by the 5-HT7 receptor based on several agonist/antagonists that were used [3].

Analytical, diagnostic and therapeutic context of HTR7

• In the present study, we tested the ability of MDMA and fenfluramine treatment to alter the ability of the circadian clock to reset in response to an agonist of the 5-HT1A and 5-HT7 receptor subtypes soon after treatment with the drugs, and then again at 20 weeks [26].
• The selective serotonin reuptake inhibitor citalopram, a widely used antidepressant, decreased immobility in both 5-HT7+/+ and 5-HT7-/- mice in the tail suspension test, suggesting that it utilizes an independent mechanism [10].
• RESULTS: RT-PCR revealed the presence of a 5-HT7 receptor mRNA in CEPI-17-CL4 cells [27].
• Western blot analysis revealed the presence of immunoreactive bands corresponding to the human 5-HT7 receptor in extracts of MC-3 cells [28].
• Sequence analysis revealed the presence of a single message that matched the sequence of the cloned human 5-HT7 receptor [29].

References