薬理と治療

Abstract

All living organisms have evolved from a hyperthermophilic common ancestor （Commonote）, which was proposed by Woese, and then, even in low optimal growth temperatures, some creatures can survive by maintaining plasma membrane fluidity. Various creatures, from microorganisms to mammals, that grow and survive in a cold environment defend themselves from the cold-induced reduction in their plasma membrane fluidities by increasing the EPA concentration in their membrane. A cold stimulus activates desaturases in the tissues of organisms, resulting in production of a considerable amount of EPA and elevating plasma membrane EPA concentrations. In cold ambient temperatures, TRPM8 is activated at higher temperatures by reduced plasma membrane fluidity. Furthermore, a cold stimulus activates the sympathetic nervous system; increases blood pressure, heart rate, and blood noradrenalin levels; decreases blood TG levels; and caused abnormal electrocardiograms and hypercoagulable state. Heat is produced by accelerated β-oxidation. The parasympathetic nervous system is also activated to counteract the excessive sympathetic nervous system activation. A cold environment causes a chronic inflammatory state and hypercoagulable state that consists of increases in blood fibrinogen and platelet aggregation. As a result, cardiovascular diseases are aggravated, and cardiovascular events occur at a higher frequency in the winter.In contrast, in a normothermic environment, the well-known actions of EPA includeincreased membrane fluidity, decreased blood TG levels, stimulation of beta-oxidation, parasympathetic system activation, improvements in abnormal electrocardiograms, and inhibition of chronic inflammation, hypercoagulation and cardiovascular diseases. Interestingly, a number of targets of these actions of EPA correspond respectively to the biological phenomena changed by cold temperatures. Therefore, it is presumed that EPA can affect cold-related changes in analogy using Gnomonic Structure. This analogy is supported by the fact that EPA increases membrane fluidity, inhibits platelet aggregation and decreases blood TG not only in non-cold conditions but also in cold conditions like Greenland. The various actions of EPA, which have been confirmed in a normothermic environment, are analogically considered to regulate various changes in a cold environment. In other words, the intrinsic role of EPA is suggested as protection of the organism from cold via a number of different actions. Various biological activities of EPA, originating from this defense against the cold, have been recognized as the diverse actions of EPA in a normothermic environment. This hypothesis might explain the diversity of actions of EPA.