Cardiotonic Steroids as Potential Endogenous Regulators in the Nervous System

Abstract

The group of compounds of the cardiotonic steroid (CTS) class includes steroid compounds that inhibit Na⁺,K⁺-ATPase. Recently, a large amount of data has been accumulating on the important role of CTS in regulating brain function through binding to Na⁺,K⁺-ATPase, which can perform a receptor role and trigger intracellular signaling cascades. Interestingly, it is in the brain where the greatest diversity of Na⁺,K⁺-ATPase isoforms different in their affinity for compounds of this class is observed. Despite the abundance of data on the presence of endogenous CTS in mammalian organisms and the evolutionary prerequisites for their existence, the presence of specific compounds is being actively discussed in the scientific literature, and enzymes directly involved in the synthesis of these compounds have not been identified. This review describes currently established functions of cardiotonic steroids and gives a detailed description of currently existing prerequisites of the endogenous origin of CTS in mammals. Experimental evidence of the presence of specific CTS in the body is given and attention is paid to the methods based on which the structure of endogenous CTS is established or predicted. We discuss why CTS can be important endogenous regulators in the nervous system and why the problem of isolating endogenous CTS from the brain and establishing their structure is urgent.