Serotonin 5-HT7 receptor

Stam NJ, et al. Human serotonin 5-HT7 receptor cloning and pharmacological characterisation of two receptor variants. FEBS Lett 1997 413(3) 489-494. 

Mahe C, Bernhard M, Bobimac I, et al. Functional expression of the serotonin 5-HT7 receptor in human glioblastoma cell lines. Br J Pharmacol 2004 143 404-410. 

Holmberg P, Sohn D, Leideborg R, et al. Novel 2-aminotetralin and 3-aminochro-man derivatives as selective serotonin 5-HT7 receptor agonists and antagonists. J Med Chem 2004 47 3927-3930. 

Ishine T, Bouchelet I, Hamel E, Lee TJF. Serotonin 5-HT7 receptors mediate relaxation of porcine pial veins. Am J Physiol Heart Circ Physiol 2000 278 H907-H907. 

Enterochromaffin cells are interspersed with mucosal cells mainly in the stomach and small intestine. In the blood, serotonin is present at high concentrations in platelets, which take up serotonin from the plasma by an active transport process. Serotonin is released on platelet activation. In the central nervous system, serotonin serves as a transmitter. The main serotonin-containing neurons are those clustered in form of the Raphe nuclei. Serotonin exerts its biological effects through the activation of specific receptors. Most of them are G-protein coupled receptors (GPCRs) and belong to the 5-HTr, 5-HT2-, 5-HT4-, 5-HTs-, 5-HT6-, 5-HT7-receptor subfamilies. The 5-HT3-receptor is a ligand-operated ion channel. 

Serotonin shares with other neurotransmitters the ability to promote W and to suppress REMS. However, 5-HT participates in a variety of functions in addition to regulation of the behavioral state. Thus, as depicted in Tables 9.4-9.8, 5-HTia, 5-HTib, 5-HT2A/2C. 5-HT3, and 5-HT7 receptors are present in structures that... 

Three families of serotonin receptor, the 5-HT family, the 5-HT2 family and the family that includes the 5-HT4, 5-ht6 and 5-HT7 receptors represent the three major classes of 5-HT receptor that are G-protein-coupled receptors (Ch. 19). The 5-HT3 receptor is a ligand-gated ion channel and is a separate family. Although each serotonin receptor can be potently activated by 5-HT, differences insignal transduction mechanisms,neuroanatomical distribution and affinities for synthetic chemicals create opportunities for drug discovery and make each 5-HT receptor subtype a potential therapeutic target. 

Hedlund PB, Danielson PE, Thomas EA, Slanina K, Carson MJ, SutcUffe JG (2003) No hypothermic response to serotonin in 5-HT7 receptor knockout mice. Proc Natl Acad SciUS A 100 1375-1380... 

HT interacts with a large diversity of G-protein-coupled receptors, namely the 5-HTi,2,4,5,6 and 7 families, and in addition with a ligand-gated cationic channel, 5-HT3. The diversity has been explained by the fact that serotonin is one of the oldest neurotransmitters in evolution. The 5-HTi receptor family (5-HTia,ib,id,ie andiF) couples mainly to Gi/o. 5-1 I I oa, 5-HT2B and 5-HT2C receptors couple to Gq/11. 5-HT4, 5-HT6, and 5-HT7 receptors couple to Gs. The 5-HT5A receptor couples principally to Gi/o. The 5-HTsb receptor seems to occur only in rodents, and no transduction mechanism has been identified. 

Erdmann J, Nothen MM, Shimron-Abarbanell D, et al. The human serotonin 7 (5-HT7) receptor gene genomic organization and systematic mutation screening in schizophrenia and bipolar affective disorder. Mol Psychiatry 1996 1 392-397. 

Lieb K, Biersack L, Waschbisch A, et al. 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. J Neurochem 2005 93 549-559. 

The above-outlined results seemed to identify the 5-HT4 receptor as the sub-type responsible for the serotonin-induced suppression of the sAHP. However, subsequent experiments conducted in the CA3 region of the hippocampus indicated that saturating concentrations of the 5-HT4 antagonist GR-113808 could not completely suppress the 5-HT-induced reduction in the AHP. Equally surprising, the administration of 5-CT, which displays little affinity for 5-HT4 receptors, mimicked the effect of serotonin on the sAHP (12). These results pointed out to the involvement of a second 5-HT receptor subtype in the modulation of the sAHP. A careful pharmacological analysis of this response, including the use of the then newly developed selective 5-HT7 receptor antagonist... 

Fig 2 5-HT receptors depolarize thalamic neurons by facilitating Ih. (A) Administration of 5-HTdepolarizes a neuron of the anterodorsal thalamic nucleus. This effect is mediated by the activation of 5-HT7 receptors (see text). (B) In these same cells, 5-HT shifts the voltage dependence of Ih in the depolarizing direction. (C) The serotonin-induced inward current, which mediates the depolarization, is inhibited by the Ih blocker ZD 7288. 

A second tantalizing possibility is that 5-HT7 receptors might be able to influence neurotransmitter release via their effects on Ih. This possibility is suggested by the observation that serotonin facilitates synaptic transmission via Ih in the crayfish neuromuscular junction (43). However, enthusiasm for this idea must be tempered by results obtained in the calyx of Held, an experimentally accessible giant mammalian synapse. Work therein has shown that facilitation of Ih by cAMP within these presynaptic terminals is without effect on neurotransmitter release (44). Thus, further work will be needed to assess the physiological significance of this possibility. 

Hery M, Francois-Bellan AM, Hery F, Deprez P, Becquet D. Serotonin directly stimulates luteinizing hormone-releasing hormone release from GT1 cells via 5-HT7 receptors. Endocrine 1997 7 261-265. 

Laplante P, Diorio J, Meaney MJ. Serotonin regulates hippocampal glucocorticoid receptor expression via a 5-HT7 receptor. Brain Res Dev Brain Res 2002 139 199-203. 

All three compounds have relatively high affinity to serotonin 5-HT2B receptors, and clozapine and olanzapine also have remarkable affinity to 5-HT6 and 5-HT7 receptors, but almost nothing is known of the role of these interactions either in the antipsychotic action or in the side effects. 

Cushing DJ, Zgombick JM, Nelson DL, et al. LY215840, a high-affinity 5-HT7 receptor ligand blocks serotonin-induced relaxation in canine coronary artery, J Pharmacol ExpTher 1996 277 1560-1566. 

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) activates at least seven distinct (5-HTi to 5-HT7) receptors in the central and peripheral nervous systems to produce important modulatory effects. With the exception of the 5-HT3 receptor, all 5-HT receptors are members of the G protein-coupled receptor family that function through adenylyl cyclase or phospholipase C second messengers. The 5-HT3 receptor, however, is a member of the superfamily of Ugand-gated ion channels and serves to moderate neuronal depolarization by increasing the flux of Na-", K-", and Ca + [8]. 

---