Disease relevance of Htr7

• 5-HT7 immunolabelling is localized mainly in the two superficial laminae of the dorsal horn and in small and medium-sized dorsal root ganglion cells, which is consistent with a predominant role in nociception [1].
• In the in vivo rat model, 5-HT2a antagonist ketanserin, 5-HT7 agonist 5-carboxamidotryptamine, and (to a limited extent) 5-HT3 antagonist ondansetron could all, like epinastine, block bronchospasm, but the "classic" antihistamine chlorpheniramine was ineffective [2].
• The above results suggest that hypotension induced via 5-HT7 receptor activation was exclusively caused by vasodilatation of the systemic vasculature, confined to skeletal muscle, carcass, mesentery/pancreas and adrenal vascular beds [3].
• Therefore, the present results are consistent with the notion that 5-HT acts on both 5-HT(1A) and 5-HT7 receptors in the AVPO to induce hypothermia, during hypoxia [4].
• The present experiments demonstrate that central 5-HT7 receptors are involved in the vagal bradycardia evoked during the cardiopulmonary reflex, baroreflexes and the chemoreflex, as well as other autonomic changes caused by these reflexes [5].

Psychiatry related information on Htr7

• 5-HT7 antisense oligonucleotide administration did not affect exploratory or locomotor activity in photocell activity monitors on day 4 or elevated plus-maze behaviour on day 6 of intracerebroventricular treatment [6].
• This work aimed to evaluate further the role of 5-HT7 receptors during memory formation in an autoshaping Pavlovian/instrumental learning task [7].
• Finally, pharmacological stimulation of 5-HT7 receptors reversed scopolamine- or dizocilpine-induced amnesia and receptor down-regulation [8].
• Importantly, this 5-HT7 receptor agonist AS 19 appears to represent a step forward respect to the notion that potent and selective 5-HT7 receptor agonists can be useful in the treatment of dysfunctional memory in aged-related decline and Alzheimer's disease [7].

High impact information on Htr7

• Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation [9].
• The deduced amino acid sequence of the 5-HT7 receptor displays limited homology with that of other 5-HT receptors [9].
• The 5-HT7 receptor, stably expressed in transfected CHO cells, bound [3H]5-HT with high affinity (Kd = 1 nM), like receptors of the 5-HT1 subfamily from which, however, it was clearly distinguished by its pharmacology [9].
• In addition to the seven stretches of hydrophobic amino acids that characterize the superfamily of receptors interacting with guanine nucleotide-binding proteins, the 448-aa sequence of the 5-HT7 receptor contains a hydrophobic domain located at its N-terminal end [9].
• Enhanced [35S]GTPgammaS binding was not detected in the presence of 5-HT1F, 5-HT2, 5-HT4, and 5-HT7 receptor agonists [10].

Chemical compound and disease context of Htr7

• 2. Haloperidol (2 mg kg(-1) i.p.) injected 5 min prior and 55 min post MDMA (15 mg kg(-1) i.p.) abolished the acute MDMA-induced hyperthermia and attenuated the neurotoxic loss of 5-HT 7 days later [11].
• Intravenous injections of 5-HT and 5-carboxamidotryptamine (5-CT) elicited a dose-dependent hypotension that was dose-dependently antagonised by (R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl) ethyl] pyrrolidine (SB-269970; a selective 5-HT7 receptor antagonist), but not by saline [12].
• However, high concentrations (> 200 nM) may enhance neurogenic inflammation, possibly by activation of 5-HT7 receptors, which may explain lack of migraine relief and excessive injection site pain in 20-30% of patients treated with sumatriptan [13].

Biological context of Htr7

• COS-7 cells transiently transfected with the GPRFO cDNA acquire saturable high-affinity binding sites for [3H]serotonin (KD = 41 nM) [14].
• This effect of 5-CT on [3H]5-HT overflow was antagonized by the 5-HT7 receptor antagonist SB-258719 (10 microM) and the 5-HT(1B/1D) antagonist SB-216641 (1 microM), the IC50 values for 5-CT in the presence of SB-258719 and SB-216641 were 94.23 +/- 4.84 and 47.81 +/- 4.66 nM [15].
• Tiospirone (TSP) is a 5-HT2 receptor antagonist with affinity for D2, 5-HT1a, and 5-HT7, and sigma receptors, which can decrease consumption of ethanol while increasing food intake [16].
• (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide (10 microm), an agonist for 5-HT1A and 5-HT7 receptors, did not facilitate the EPSP. alpha-Methyl-5-HT (10 microm), a 5-HT2 receptor agonist, increased the amplitude of the EPSC [17].
• These results challenge a previous report and suggest that the proposed down-regulation of 5-HT7 receptors after fluoxetine treatment should be considered with caution [18].

Anatomical context of Htr7

• Pre- and postsynaptic localization of the 5-HT7 receptor in rat dorsal spinal cord: immunocytochemical evidence [1].
• In dendrites, the labelling is localized on synaptic differentiations, suggesting that 5-HT may act synaptically on the 5-HT7 receptor [1].
• This indicates that 5-HT7 receptors have a potential significance in the rat hypothalamus during early postnatal development [19].
• A 5-HT7 heteroreceptor-mediated inhibition of [3H]serotonin release in raphe nuclei slices of the rat: evidence for a serotonergic-glutamatergic interaction [15].
• Consistent with the RNA blot data, GPRFO mRNA has been detected by in situ hybridization in the centrolateral, central medial, and intermediodorsal thalamic nuclei [14].

Associations of Htr7 with chemical compounds

• The antagonist effect of SB-258719 (10 microM) on 5-CT-evoked [3H]5-HT overflow inhibition was also determined in the presence of 1 microM SB-216641 or 1 microM SB-216641 and 10 microM WAY-100635, and additive interactions were found between the antagonists of 5-HT7 and 5-HT1 receptor subtypes [15].
• We therefore speculated that the axon terminals of the glutamatergic cortico-raphe neurons may possess 5-HT7 receptors that inhibit glutamate release, which consequently leads to decreased activity of serotonergic neurons [15].
• We found that the 5-HT1 and 5-HT7 agonists 5-carboxamidotryptamine (5-CT) and 5-methoxytryptamine mimicked the response to 5-HT, whereas the 5-HT2 agonist 2,5-dimethoxy-4-iodoamphetamine did not [20].
• We found that the 5-HT7 ligands ritanserin, methylsergide, LSD, and mesulergine could inhibit the 5-HT-induced inward current, whereas the 5-HT1 antagonist cyanopindolol had no effect [20].
• Pronociceptive role of peripheral and spinal 5-HT7 receptors in the formalin test [21].

Regulatory relationships of Htr7

• Coupling of neuronal 5-HT7 receptors to activation of extracellular-regulated kinase through a protein kinase A-independent pathway that can utilize Epac [22].
• The pharmacological profile of the receptor on thalamic/hypothalamic astrocytes suggests that the 5-HT7 receptor is the dominant receptor that is functionally expressed even though astrocyte cultures have the capacity to express both 5-HT6 and 5-HT7 receptor messenger RNA [23].

Other interactions of Htr7

• Localization of 5-HT2A, 5-HT3, 5-HT5A and 5-HT7 receptor-like immunoreactivity in the rat cerebellum [24].
• These findings indicate that 5-CT inhibits [3H]5-HT overflow from raphe nuclei slices of the rat by stimulation of 5-HT7 and 5-HT(1B/1D receptors, whereas the role of 5-HT1A receptors in this inhibition is less pronounced [15].
• Collectively, these data suggest that ventilatory LTF requires 5-HT2 receptors and that the CIH effect on LTF requires non-5-HT2 serotonin receptors, probably 5-HT6 and/or 5-HT7 subtype(s) [25].
• In contrast, chronic stress (1 week of variable stressors) had little effect on hippocampal 5-HT7 receptor mRNA (9% rise in CA3) but decreased MR mRNA (e.g. 34% decrease in CA2) and GR mRNA expression selectively in the dentate gyrus (26% decrease) [26].
• Six days of intracerebroventricular 5-HT7 antisense oligonucleotide treatment significantly reduced [3H]5-HT binding to hypothalamic 5-HT7 receptors, whereas cortical 5-HT2C density remained unchanged [6].

Analytical, diagnostic and therapeutic context of Htr7

• Neuronal cultures were prepared from postnatal pups P2, P3 and P5, were treated with bFGF and processed by means of immunofluorescence technique using a polyclonal 5-HT7 receptor antibody [19].
• Since these cells expressed 5-HT7 receptor mRNA, as determined by single-cell reverse transcriptase-polymerase chain reaction, we pharmacologically characterized the 5-HT receptor mediating this response [20].
• It was observed that dexamethasone treatment (1-100 nM, 3-72 h) also decreased the expression of 5-HT7 receptor mRNA, using reverse transcription and polymerase chain reaction analysis [27].
• 5-HT7 receptor mRNA was increased in CA1 and CA3b after adrenalectomy, with no alterations in other hippocampal subfields or in retrosplenial cortex [28].
• Certainly, reservations regarding the selectivity of AS 19 for 5-HT7 and other 5-HT receptors in vivo are noteworthy and, therefore, its validity for use in animal models as a pharmacological tool [7].

References