K4 Elite
K4 Elite
Apelin-13 is a 13-amino-acid endogenous peptide fragment and agonist of the APJ (apelin) receptor, studied extensively in isolated-heart, cardiomyocyte and rodent models of cardiac contractility, vascular tone and fluid balance.
Apelin-13 is one of several naturally occurring fragments processed from the 77-amino-acid preproapelin precursor. It was identified as the endogenous ligand of APJ, a G protein-coupled receptor that had previously been characterised only as an orphan receptor structurally related to the angiotensin AT1 receptor.
The apelin/APJ axis is expressed in cardiomyocytes, vascular endothelium, hypothalamus and several peripheral tissues, which is why the literature on this peptide spans cardiovascular physiology, fluid homeostasis and metabolic signalling. A pyroglutamyl-modified variant, [Pyr1]-Apelin-13, is the predominant circulating isoform in human plasma and is frequently used in place of the unmodified peptide in laboratory work because of its greater resistance to aminopeptidase degradation.
Research interest is largely mechanistic. Published work characterises receptor pharmacology, signalling bias, degradation by angiotensin-converting enzyme 2 (ACE2), and physiological responses in isolated tissue and animal models. This material is a summary of that published literature and is provided for research reference only.
Apelin-13 binds APJ, a class A GPCR that couples primarily to Gi/Go and also recruits beta-arrestin. Reported downstream events in cardiac preparations include phospholipase C and protein kinase C activation, ERK1/2 phosphorylation, activation of the sarcolemmal Na+/H+ exchanger with a rise in intracellular pH, and increased myofilament calcium sensitivity by way of myosin light chain kinase.
In isolated rat ventricular myocytes, investigators reported that apelin did not measurably alter L-type calcium current or voltage-activated potassium currents, which is one reason the contractile response has been attributed to calcium-sensitisation and exchanger-mediated mechanisms rather than to increased calcium influx. Apelin-13 is a substrate for ACE2, which cleaves the C-terminal phenylalanine and is a principal route of peptide inactivation in the literature.
Isolated perfused rat heart (Szokodi et al., 2002). Species/model: ex vivo perfused adult rat heart. Measure: developed contractile force. Investigators reported a concentration-dependent positive inotropic response over a picomolar-to-nanomolar concentration range, with a reported EC50 in the low picomolar range; inhibition of phospholipase C and protein kinase C markedly attenuated the response [1].
Adult rat cardiomyocytes (Perjes et al., 2014). Species/model: isolated adult rat ventricular myocytes and perfused hearts. Measure: sarcomere shortening and kinase phosphorylation. The authors reported that the contractile response proceeded through parallel and independent activation of PKC-epsilon and ERK1/2 [2].
Isolated ventricular myocyte electrophysiology (Farkasfalvi et al., 2007). Species/model: isolated adult rat and failing human ventricular myocytes. Measure: sarcomere shortening, ion currents, intracellular pH. Apelin at 1 nM increased sarcomere shortening and activated the Na+/H+ exchanger, while L-type calcium current and voltage-activated potassium currents were not measurably changed [3].
Stabilised analogue characterisation (2025). Species/model: cellular electrophysiology. Measure: transient outward potassium current (Ito). A metabolically stabilised apelin-13 analogue was characterised as a potent Ito blocker, and the authors discussed the finding in the context of inherited arrhythmia models [4].
Combinations examined in the research literature. Descriptive only — not a recommendation to combine compounds.