Trends in Pharmacological Sciences
Unravelling the roles of the apelin system: prospective therapeutic applications in heart failure and obesity
Section snippets
Characterization of the apelin system
The gene that encodes the apelin receptor (which was known previously as the APJ receptor) was discovered first by homology-cloning methods and it shares greatest sequence identity (54% in the transmembrane regions) with the angiotensin AT1 receptor [1]. Similar to many newly identified G-protein-coupled receptors (GPCRs), the absence of an immediately apparent endogenous ligand limited further characterization and, thus, the apelin receptor was added to a growing number of ‘orphan’ GPCRs that
A potent inotropic agent with cardioprotective properties
As predicted by the high levels of cardiovascular expression of apelin and its receptor and the well characterized role of angiotensin II on the circulatory system, the importance of apelin in modulating blood pressure and cardiac function is being revealed. For example, the density of apelin-binding sites in human and rat myocardium is comparable to that of the AT1 receptor [28]. When administered to isolated rat hearts, apelin is one of the most potent endogenous positive inotropic
Novel hypotensive action of apelin
Apelin modulates the contractility of blood vessels, which has the overall effect of lowering blood pressure. That apelin-13 regulates blood pressure was shown first following intravenous (i.v.) injection of 1 μg and 2 μg in anaesthetized rats, which resulted in a transient drop in mean arterial blood pressure (MABP) of ∼12 mmHg with no change in heart rate [5]. These results have been confirmed subsequently by studies in which injection of 10 nmol kg−1 apelin-12, apelin-13 and apelin-36 decreased
Apelin, obesity and the adipoinsular axis
The reported distribution of apelin and the apelin receptor in the hypothalamus, gastric mucosa and fat cells has led to the suggestion that the apelin system has roles in modulating appetite, digestion and metabolism following food intake. Whether apelin acts in the CNS to modulate feeding behaviour is controversial. Administration of apelin-13 by i.c.v., but not i.v., injection decreases food intake in both fed and starved rats [38]. Another report has observed similar effects when apelin is
Conclusions and future perspectives
Although the apelin receptor was discovered more than a decade ago, functional characterization of the apelin system began only recently following the identification of its endogenous ligands. Since its discovery as a mediator of the effects of the rennin–angiotensin system in 1940, the elucidation of the angiotensin system has revealed enormous complexity, with roles in diverse physiological mechanisms such as blood-pressure regulation, body-water balance, and hypothalamic functions documented
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2021, Clinica Chimica Acta[MeArg<sup>1</sup>, NLe<sup>10</sup>]-apelin-12: Optimization of solid-phase synthesis and evaluation of biological properties in vitro and in vivo
2020, PeptidesCitation Excerpt :This work continues our research on synthesis and study of properties of the peptide M. Its goals are (i) the development of an optimized method for Fmoc solid-phase peptide synthesis (SPPS) of peptide M, (ii) a comparative assessment of the proteolytic stability of this peptide and natural apelin-12 in human blood plasma by 1H NMR technique and (iii) the study of the effect of infusion of these peptides on the heart function in rabbits with cardiomyopathy. The last goal of our work was initiated by studies showing the prominent role of the apelin-APJ system in the pathogenesis of heart failure [2,3] and the ability of exogenous apelin-13 to improve LV function in animals and humans with this pathology [20–23]. We used a chemotherapeutic drug doxorubicin (Dox) as a cumulative cardiotoxic agent causing cardiomyopathy [24].
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