Purinergic signalling plays a crucial role in proper functioning of the nervous system. Mechanisms depending on extracellular nucleotides and their P2 receptors also underlie a number of nervous system dysfunctions. This review aims to present the role of purinergic signalling, with particular focus devoted to role of P2 family receptors, in epilepsy, depression, neuropathic pain, nervous system neoplasms, such as glioma and neuroblastoma, neurodegenerative diseases like Parkinson’s disease, Alzheimer’s disease and multiple sclerosis. The above-mentioned conditions are associated with changes in expression of extracellular ectonucleotidases, P2X and P2Y receptors in neurons and glial cells, as well as releasing considerable amounts of nucleotides from activated or damaged nervous tissue cells into the extracellular space, which contributes to disturbance in purinergic signalling. The numerous studies indicate a potential possibility of using synthetic agonists/antagonists of P2 receptors in treatment of selected nervous system diseases. This is of particular significance, since numerous available agents reveal a low effectiveness and often produce side effects.

CD36 is a multiligand receptor contributing to glucose and lipid metabolism, immune response, inflammation, thrombosis, and fibrosis. A wide range of tissue expression includes cells sensitive to metabolic abnormalities associated with metabolic syndrome and diabetes mellitus (DM), such as monocytes and macrophages, epithelial cells, adipocytes, hepatocytes, skeletal and cardiac myocytes, pancreatic β-cells, kidney glomeruli and tubules cells, pericytes and pigment epithelium cells of the retina, and Schwann cells. These features make CD36 an important component of the pathogenesis of DM and its complications, but also a promising target in the treatment of these disorders. The detrimental effects of CD36 signaling are mediated by the uptake of fatty acids and modified lipoproteins, deposition of lipids and their lipotoxicity, alterations in insulin response and the utilization of energy substrates, oxidative stress, inflammation, apoptosis, and fibrosis leading to the progressive, often irreversible organ dysfunction. This review summarizes the extensive knowledge of the contribution of CD36 to DM and its complications, including nephropathy, retinopathy, peripheral neuropathy, and cardiomyopathy.

Adiponectin is the adipokine associated with insulin sensitization, reducing liver gluconeogenesis, and increasing fatty acid oxidation and glucose uptake. Adiponectin is present in the kidneys, mainly in the arterial endothelium and smooth muscle cells, as well as in the capillary endothelium, and might be considered as a marker of many negative factors in chronic kidney disease. The last few years have brought a rising body of evidence that adiponectin is a multipotential protein with anti-inflammatory, metabolic, anti-atherogenic, and reactive oxygen species (ROS) protective actions. Similarly, adiponectin has shown many positive and direct actions in kidney diseases, and among many kidney cells. Data from large cross-sectional and cohort studies showed a positive correlation between serum adiponectin and mortality in chronic kidney disease. This suggests a complex interaction between local adiponectin action, comorbidities, and uremic milieu. In this review we discuss the role of adiponectin in chronic kidney disease.

Purinergic signaling in the nervous system has been the focus of a considerable number of studies since the 1970s. The P2X and P2Y receptors are involved in the initiation of purinergic signaling. They are very abundant in the central and peripheral nervous systems, where they are expressed on the surface of neurons and glial cells - microglia, astrocytes, oligodendrocytes and Schwann cells and the precursors of the latter two. Their ligands - extracellular nucleotides - are released in the physiological state by astrocytes and neurons forming synaptic connections, and are essential for the proper functioning of nervous system cells. Purinergic signaling plays a crucial role in neuromodulation, neurotransmission, myelination in the CNS and PNS, intercellular communication, the regulation of ramified microglia activity, the induction of the response to damaging agents, the modulation of synaptic activity and other glial cells by astrocytes, and the induction of astrogliosis. Understanding these mechanisms and the fact that P2 receptors and their ligands are involved in the pathogenesis of diseases of the nervous system may help in the design of drugs with different and more effective mechanisms of action.

The imbalanced network of adipokines may contribute to the development of systemic low-grade inflammation, metabolic diseases and coronary artery disease (CAD). In the last decade, three classic adipokines—adiponectin, leptin and resistin—have been of particular interest in studies of patients with CAD due to their numerous properties in relation to the cardiovascular system. This has directed our attention to the association of adipokines with cardiac structure and function and the development of heart failure (HF), a common end effect of CAD. Thus, the purpose of this study was to analyse the associations of plasma concentrations of adiponectin, leptin and resistin with parameters assessed in the echocardiographic examinations of CAD patients. The presented study enrolled 167 Caucasian patients (133 male; 34 female) with CAD. Anthropometric, echocardiographic and basic biochemical measurements, together with plasma concentrations of adiponectin, leptin and resistin assays, were performed in each patient. Adiponectin concentrations were negatively associated with left ventricular ejection fraction (LVEF) and shortening fraction (LVSF), and positively associated with mitral valve E/A ratio (E/A), left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter LVESD, and left atrium diameter (LAD). Resistin concentrations were negatively associated with E/A. Leptin concentrations, although correlated with HF severity assessed by the New York Heart Association (NYHA) Functional Classification, were not independently associated with the echocardiographic parameters of cardiac structure or function. In conclusion, adiponectin and resistin, but not leptin, are associated with the echocardiographic parameters of cardiac remodelling and dysfunction. These associations suggest that adiponectin and resistin might be involved in mechanisms of cardiac remodelling or compensative response. We also suggest the possible benefits of adiponectin and resistin level measurements in the monitoring of patients with CAD.