Inotropic action of the puberty hormone kisspeptin in rat, mouse and human: cardiovascular distribution and characteristics of the kisspeptin receptor

Kisspeptins, the ligands of the kisspeptin receptor known for its roles in reproduction and cancer, are also vasoconstrictor peptides in atherosclerosis-prone human aorta and coronary artery. The aim of this study was to further investigate the cardiovascular localisation and function of the kisspep...

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Published in:PloS one 2011-11, Vol.6 (11), p.e27601
Main Authors: Maguire, Janet J, Kirby, Helen R, Mead, Emma J, Kuc, Rhoda E, d'Anglemont de Tassigny, Xavier, Colledge, William H, Davenport, Anthony P
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Amino acids
Animal tissues
Animals
Aorta
Aorta - drug effects
Aorta - metabolism
Arteriosclerosis
Atherosclerosis
Atria
Biology
Blood vessels
Cancer
Cardiomyocytes
Cardiomyopathy
Cardiotonic Agents - pharmacology
Cardiovascular System - drug effects
Cardiovascular System - metabolism
Coronary artery
Coronary artery disease
Coronary vessels
Disruption
Endothelium
Endothelium, Vascular - drug effects
Endothelium, Vascular - metabolism
Female
Gene Expression Regulation - drug effects
Heart
Heart Atria - drug effects
Heart Atria - metabolism
Heart diseases
Heart Diseases - metabolism
Heart Diseases - pathology
Heart transplantation
Hormones
Human behavior
Human subjects
Humans
Immunohistochemistry
In Vitro Techniques
Kiss1 protein
Kisspeptins - pharmacology
Localization
Male
Medicine
Mice
Microscopy
Middle Aged
Myocardium
Myocardium - metabolism
Myocytes
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Neurosciences
Peptides
Pharmacology
Physiological aspects
Physiology
Preeclampsia
Pregnancy
Protein Transport - drug effects
Proteins
Puberty
Puberty - drug effects
Quantitative analysis
Radioimmunoassay
Rats
Receptor density
Receptor mechanisms
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
Reproductive disorders
RNA, Messenger - genetics
RNA, Messenger - metabolism
Rodents
Smooth muscle
Vasoconstriction - drug effects
Young Adult
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Summary:Kisspeptins, the ligands of the kisspeptin receptor known for its roles in reproduction and cancer, are also vasoconstrictor peptides in atherosclerosis-prone human aorta and coronary artery. The aim of this study was to further investigate the cardiovascular localisation and function of the kisspeptins and their receptor in human compared to rat and mouse heart. Immunohistochemistry and radioligand binding techniques were employed to investigate kisspeptin receptor localisation, density and pharmacological characteristics in cardiac tissues from all three species. Radioimmunoassay was used to detect kisspeptin peptide levels in human normal heart and to identify any pathological changes in myocardium from patients transplanted for cardiomyopathy or ischaemic heart disease. The cardiac function of kisspeptin receptor was studied in isolated human, rat and mouse paced atria, with a role for the receptor confirmed using mice with targeted disruption of Kiss1r. The data demonstrated that kisspeptin receptor-like immunoreactivity localised to endothelial and smooth muscle cells of intramyocardial blood vessels and to myocytes in human and rodent tissue. [(125)I]KP-14 bound saturably, with subnanomolar affinity to human and rodent myocardium (K(D) = 0.12 nM, human; K(D) = 0.44 nM, rat). Positive inotropic effects of kisspeptin were observed in rat, human and mouse. No response was observed in mice with targeted disruption of Kiss1r. In human heart a decrease in cardiac kisspeptin level was detected in ischaemic heart disease. Kisspeptin and its receptor are expressed in the human, rat and mouse heart and kisspeptins possess potent positive inotropic activity. The cardiovascular actions of the kisspeptins may contribute to the role of these peptides in pregnancy but the consequences of receptor activation must be considered if kisspeptin receptor agonists are developed for use in the treatment of reproductive disorders or cancer.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0027601