International Union of Basic and Clinical Pharmacology. LXXVII. Kisspeptin Receptor Nomenclature, Distribution, and Function

Kirby, Helen R.; Maguire, Janet J.; Colledge, William H; Davenport, Anthony P.

doi:10.1124/pr.110.002774

Cited by 89 publications

(88 citation statements)

References 173 publications

(230 reference statements)

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“…However, the failure of the KP receptor antagonist, KP receptor knockdown with siRNA, and the NPFF antagonist to block these responses raises questions about the mechanism of action. The receptor antagonists used in this study target the receptors that KP is known to act on; 46 however, it is possible that there are other receptors that can be activated by KP. An alternative mechanism of action could be a direct binding interaction between KP and the Aβ, PrP, or IAPP peptides, and we therefore sought to determine if KP does indeed bind these amyloid peptides.…”

mentioning

confidence: 99%

Kisspeptin Prevention of Amyloid-β Peptide Neurotoxicityin Vitro

Milton

Chilumuri

Rocha‐Ferreira

et al. 2012

ACS Chem. Neurosci.

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Alzheimer's disease (AD) onset is associated with changes in hypothalamic-pituitary−gonadal (HPG) function. The 54 amino acid kisspeptin (KP) peptide regulates the HPG axis and alters antioxidant enzyme expression. The Alzheimer's amyloid-β (Aβ) is neurotoxic, and this action can be prevented by the antioxidant enzyme catalase. Here, we examined the effects of KP peptides on the neurotoxicity of Aβ, prion protein (PrP), and amylin (IAPP) peptides. The Aβ, PrP, and IAPP peptides stimulated the release of KP and KP 45−54. The KP peptides inhibited the neurotoxicity of Aβ, PrP, and IAPP peptides, via an action that could not be blocked by kisspeptin-receptor (GPR-54) or neuropeptide FF (NPFF) receptor antagonists. Knockdown of KiSS-1 gene, which encodes the KP peptides, in human neuronal SH-SY5Y cells with siRNA enhanced the toxicity of amyloid peptides, while KiSS-1 overexpression was neuroprotective. A comparison of the catalase and KP sequences identified a similarity between KP residues 42−51 and the region of catalase that binds Aβ. The KP peptides containing residues 45−50 bound Aβ, PrP, and IAPP, inhibited Congo red binding, and were neuroprotective. These results suggest that KP peptides are neuroprotective against Aβ, IAPP, and PrP peptides via a receptor independent action involving direct binding to the amyloid peptides. KEYWORDS: KiSS-1, kisspeptin, amyloid-β, prion protein, amylin, neuroprotection N euroendocrine hormone changes are seen in aging, and there are disease specific changes associated with Alzheimer's disease (AD). 1,2 One of the neuroendocrine systems to show profound changes with aging is the hypothalamic−pituitary−gonadal (HPG) system, and the pathology of AD, Creutzfeldt−Jakob disease (CJD), and type 2 diabetes mellitus (T2DM) is also associated with changes in the hormones of this system. 3,4 A major regulator of the HPGaxis is the 54 amino acid kisspeptin (KP) peptide, which acts on gonadotrophin-releasing hormone (GnRH) neurons to activate GnRH release. 5 The KP peptide is produced in neurons by processing of the KiSS-1 preproprotein to yield the 54 amino acid KP peptide, which corresponds to residues 68−121 of KiSS-1. 6 Shorter derivatives of KP peptide comprising the C-terminal 14 (KP 41−54), 13 (KP 42−54), and 10 (KP 45−54) amino acids have also been found in tissues and corresponding to residues 108− 121, 109−121, and 112−121 of KiSS-1. 6,7 Biological activity of KP peptides requires the KP 45−54 sequence and is mediated via a specific KP receptor (GPR-54). 6,7 Lack of KP signaling via the GPR-54 receptor is associated with reproductive system failure. 8 Cleavage of the KP 45−54 peptide between residues 51 and 52 by matrix metalloproteinases abolishes the activation of GPR-54 by the KP 45−54 peptide. 9 The KP 42−54 and KP 45−54 peptides also activate NPFF receptors, 10,11 and some of the actions of KP peptides could be mediated by NPFF receptor activation.There are profound changes in KP signaling at menopause 12 and notable sex differences in hypothalamic neurodegenera...

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mentioning

confidence: 99%

Kisspeptin Prevention of Amyloid-β Peptide Neurotoxicityin Vitro

Milton

Chilumuri

Rocha‐Ferreira

et al. 2012

ACS Chem. Neurosci.

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“…An increased locomotor activity was also observed in these experiments, however, this lasted only an hour suggesting that it is not the cause of the detected changes in temperature. As kisspeptin is a well-known stimulator of GnRH [94], GnRH might mediate the hyperthermic action of KP-13, which would be in accord with the possible role of GnRH in thermoregulation, suggesting GnRH as a causative factor in hot flashes [115,41]. Other possible explanation could involve the activation of hypothalamic prostaglandin synthesis, increased basal metabolic activity or the stimulation of the hypothalamus-pituitary-thyroid axis.…”

Section: Discussionmentioning

confidence: 79%

“…In support of KISS1R mediation stands several results. First, kisspeptin and KISS1R are expressed in neuronal structures involved in nociception signalling such as dorsal root ganglia and the dorsal horn lamina I and II of the spinal cord as well as brain regions such as hippocampus, amygdala and periaqueductal grey [94,47,140]. This pattern of expression suggests a function in pain modulation.…”

Section: Discussionmentioning

confidence: 99%

“…Kisspeptins are the product of the KISS1 gene and it must be noted that the comparison of the human, mouse and rat DNA sequences of this gene found them to be highly homologous [217]. In humans the KISS1 gene encodes a 145 amino acid long precursor peptide, which through multiple proteolytic steps will generate the major product consisting of 54 amino acids (KP-54), but its alternative cleavage can give rise to other biologically active derivatives containing 14, 13 or 10 amino acids, christened kisspeptin-14 (KP-14), kisspeptin-13 (KP-13) and kisspeptin-10 (KP-10), respectively [98,94,171] (Figure 2). Of note, there is some debate in the field concerning the possible endogenous role of the shorter products: mainly if they are generated through different proteolytic processes or rather they are a result of the degradation of the original KP-54 [217].…”

Section: Structure Of Kisspeptins and Their Receptor Targetsmentioning

confidence: 99%

“…In the central nervous system, kisspeptin is transcribed within the hippocampal dentate gyrus [94]. In the present investigation, antidepressant-like effects of KP-13 were studied and the potential involvement of the adrenergic, serotonergic, cholinergic, dopaminergic and gabaergic receptors in its antidepressant-like effects was investigated in a modified FST in mice.…”

Section: Introductionmentioning

confidence: 99%

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Kisspeptin modulates the activity of the stress system and associated behaviours, the body temperature and nociception

Csabafi¹

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Magnocellular Neurons and Posterior Pituitary Function

Brown

2016

Comprehensive Physiology

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The posterior pituitary gland secretes oxytocin and vasopressin (the antidiuretic hormone) into the blood system. Oxytocin is required for normal delivery of the young and for delivery of milk to the young during lactation. Vasopressin increases water reabsorption in the kidney to maintain body fluid balance and causes vasoconstriction to increase blood pressure. Oxytocin and vasopressin secretion occurs from the axon terminals of magnocellular neurons whose cell bodies are principally found in the hypothalamic supraoptic nucleus and paraventricular nucleus. The physiological functions of oxytocin and vasopressin depend on their secretion, which is principally determined by the pattern of action potentials initiated at the cell bodies. Appropriate secretion of oxytocin and vasopressin to meet the challenges of changing physiological conditions relies mainly on integration of afferent information on reproductive, osmotic, and cardiovascular status with local regulation of magnocellular neurons by glia as well as intrinsic regulation by the magnocellular neurons themselves. This review focuses on the control of magnocellular neuron activity with a particular emphasis on their regulation by reproductive function, body fluid balance, and cardiovascular status. © 2016 American Physiological Society. Compr Physiol 6:1701-1741, 2016.

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International Union of Basic and Clinical Pharmacology. LXXVII. Kisspeptin Receptor Nomenclature, Distribution, and Function

Cited by 89 publications

References 173 publications

Kisspeptin Prevention of Amyloid-β Peptide Neurotoxicityin Vitro

Kisspeptin Prevention of Amyloid-β Peptide Neurotoxicityin Vitro

Kisspeptin modulates the activity of the stress system and associated behaviours, the body temperature and nociception

Magnocellular Neurons and Posterior Pituitary Function

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