title: 5-HT7 receptor subtype as a mediator of the serotonergic regulation of luteinizing hormone release in the zona incerta.
abstract: 5-Hydroxytryptamine (5-HT) and the 5-HT(1A/7) receptor agonist (+)-8-hydroxy-2-(di-n-propylamino) tetralinHBr (8-OH-DPAT), injected into the zona incerta (an area in the dorsal hypothalamus) of the female rat, inhibit the release of luteinizing hormone (LH) and the effects of both are blocked by the 5-HT(2/7) receptor antagonist, ritanserin. As both 8-OH-DPAT and ritanserin have moderate activity at the 5-HT7 receptor subtype, the possibility that this subtype might mediate their effects in the zona incerta has been investigated. Ovariectomised rats were primed with 5 microg oestradiol benzoate followed at 48 h by 0.5 mg progesterone, which induces an LH surge. 5-Carboxamidotryptamine (5-CT), a potent but non-selective agonist at 5-HT7 receptors, like 5-HT and 8-OH-DPAT, inhibited the LH surge at 5 and 1.25 nmol injected bilaterally into the zona incerta. The non-selective 5-HT(2/7) receptor antagonist ritanserin and the selective 5-HT7 receptor antagonist, (R)-3-(2-(2-(4-methyl-piperidin-1-yl)-pyrrolidine-1-sulfonyl)-phenol (SB-269970-A) at 0.5 microg/side blocked all three receptor agonists when injected concurrently into the zona incerta. However, lower (0.2 microg) and higher doses (2 and 5 microg) of SB-269970-A were less effective, indicating a bell-shaped dose-response curve. SB-269970-A was also inhibitory when administered systemically (1 mg/kg intraperitoneally (i.p.)). When LH release was suppressed by 5 microg oestradiol benzoate, SB-269970-A (0.5 and 2 microg) did not elevate levels, indicating it is unlikely that 5-HT7 receptors mediate a tonic inhibition on release but rather are involved in terminating the pre-ovulatory LH surge. These data demonstrate that 5-HT7 receptors play a role in the regulation of LH by the zona incerta in rat brain.
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, Pakistan.
authors.forename: Arif
authors.initials: A
authors.lastname: Siddiqui
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Abu-Amara
authors.forename: Cyrielle
authors.initials: C
authors.lastname: Aldairy
authors.forename: James J
authors.initials: JJ
authors.lastname: Hagan
authors.forename: Catherine
authors.initials: C
authors.lastname: Wilson
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D005260:Female; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D010052:Ovariectomy; D010636:Phenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D020530:Subthalamus / Q000187:drug effects / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D010636:Phenols; D010879:Piperazines; D011985:Receptors, Serotonin; C404922:SB 269970; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; C081293:WAY 100135; D016713:Ritanserin; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007986:Luteinizing Hormone; C047087:5-carboxamidotryptamine