Dataset Information

Activation of Neuropeptide FF Receptors by Kisspeptin Receptor Ligands.

ABSTRACT: Kisspeptin is a member of the RFamide neuropeptide family that is implicated in gonadotropin secretion. Because kisspeptin-GPR54 signaling is implicated in the neuroendocrine regulation of reproduction, GPR54 ligands represent promising therapeutic agents against endocrine secretion disorders. In the present study, the selectivity profiles of GPR54 agonist peptides were investigated for several GPCRs, including RFamide receptors. Kisspeptin-10 exhibited potent binding and activation of neuropeptide FF receptors (NPFFR1 and NPFFR2). In contrast, short peptide agonists bound with much lower affinity to NPFFRs while showing relatively high selectivity toward GPR54. The possible localization of secondary kisspeptin targets was also demonstrated by variation in the levels of GnRH release from the median eminence and the type of GPR54 agonists used. Negligible affinity of the reported NPFFR ligands to GPR54 was observed and indicates the unidirectional cross-reactivity between both ligands.

SUBMITTER: Oishi S

PROVIDER: S-EPMC4018085 | biostudies-other | 2011 Jan

REPOSITORIES: biostudies-other

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Activation of Neuropeptide FF Receptors by Kisspeptin Receptor Ligands.

Oishi Shinya S Misu Ryosuke R Tomita Kenji K Setsuda Shohei S Masuda Ryo R Ohno Hiroaki H Naniwa Yousuke Y Ieda Nahoko N Inoue Naoko N Ohkura Satoshi S Uenoyama Yoshihisa Y Tsukamura Hiroko H Maeda Kei-Ichiro K Hirasawa Akira A Tsujimoto Gozoh G Fujii Nobutaka N

ACS medicinal chemistry letters 20101025 1

Kisspeptin is a member of the RFamide neuropeptide family that is implicated in gonadotropin secretion. Because kisspeptin-GPR54 signaling is implicated in the neuroendocrine regulation of reproduction, GPR54 ligands represent promising therapeutic agents against endocrine secretion disorders. In the present study, the selectivity profiles of GPR54 agonist peptides were investigated for several GPCRs, including RFamide receptors. Kisspeptin-10 exhibited potent binding and activation of neuropept ...[more]

PMID: 24900254

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Project description:Deorphanization of GPR54 receptor a decade ago led to the characterization of the kisspeptin receptor (Kissr) in mammals and the discovery of its major role in the brain control of reproduction. While a single gene encodes for Kissr in eutherian mammals including human, other vertebrates present a variable number of Kissr genes, from none in birds, one or two in teleosts, to three in an amphibian, xenopus. In order to get more insight into the evolution of Kissr gene family, we investigated the presence of Kissr in osteichthyans of key-phylogenetical positions: the coelacanth, a representative of early sarcopterygians, the spotted gar, a non-teleost actinopterygian, and the European eel, a member of an early group of teleosts (elopomorphs). We report the occurrence of three Kissr for the first time in a teleost, the eel. As measured by quantitative RT-PCR, the three eel Kissr were differentially expressed in the brain-pituitary-gonadal axis, and differentially regulated in experimentally matured eels, as compared to prepubertal controls. Subfunctionalisation, as shown by these differences in tissue distribution and regulation, may have represented significant evolutionary constraints for the conservation of multiple Kissr paralogs in this species. Furthermore, we identified four Kissr in both coelacanth and spotted gar genomes, providing the first evidence for the presence of four Kissr in vertebrates. Phylogenetic and syntenic analyses supported the existence of four Kissr paralogs in osteichthyans and allowed to propose a clarified nomenclature of Kissr (Kissr-1 to -4) based on these paralogs. Syntenic analysis suggested that the four Kissr paralogs arose through the two rounds of whole genome duplication (1R and 2R) in early vertebrates, followed by multiple gene loss events in the actinopterygian and sarcopterygian lineages. Due to gene loss there was no impact of the teleost-specific whole genome duplication (3R) on the number of Kissr paralogs in current teleosts.

Project description:BackgroundInitially identified as suppressors of metastasis in various types of cancer, kisspeptins are a family of neuropeptides that are key regulators of the mammalian reproductive axis. Accumulating evidence has shown that kisspeptin is able to control both the pulsatile and surge GnRH release, playing fundamental roles in female reproduction, which include the secretion of gonadotropins, puberty onset, brain sex differentiation, ovulation and the metabolic regulation of fertility. Furthermore, recent studies have demonstrated the involvement of the kisspeptin system in the processes of implantation and placentation. This review summarizes the current knowledge of the pathophysiological role and utility of these local placental regulatory factors as potential biomarkers during the early human gestation.Objective and rationaleA successful pregnancy, from the initiation of embryo implantation to parturition, is a complex process that requires the orchestration of a series of events. This review aims to concisely summarize what is known about the role of the kisspeptin system in implantation, placentation, early human pregnancy and pregnancy-related disorders, and to develop strategies for predicting, diagnosing and treating these abnormalities.Search methodsUsing the PubMed and Google Scholar databases, we performed comprehensive literature searches in the English language describing the advancement of kisspeptins and the kisspeptin receptor (KISS1R) in implantation, placentation and early pregnancy in humans, since its initial identification in 1996 and ending in July 2018.OutcomesRecent studies have shown the coordinated spatial and temporal expression patterns of kisspeptins and KISS1R during human pregnancy. The experimental data gathered recently suggest putative roles of kisspeptin signaling in the regulation of trophoblast invasion, embryo implantation, placentation and early pregnancy. Dysregulation of the kisspeptin system may negatively affect the processes of implantation as well as placentation. Clinical studies indicate that the circulating levels of kisspeptins or the expression levels of kisspeptin/KISS1R in the placental tissues may be used as potential diagnostic markers for women with miscarriage and gestational trophoblastic neoplasia.Wider implicationsComprehensive research on the pathophysiological role of the kisspeptin/KISS1R system in implantation and placentation will provide a dynamic and powerful approach to understanding the processes of early pregnancy, with potential applications in observational and analytic screening as well as the diagnosis, prognosis and treatment of implantation failure and early pregnancy-related disorders.

Dataset Information

Activation of Neuropeptide FF Receptors by Kisspeptin Receptor Ligands.

Publications

Activation of Neuropeptide FF Receptors by Kisspeptin Receptor Ligands.

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