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326ISSN 0022-0930, Journal of Evolutionary Biochemistry and Physiology, 2016, Vol. 52, No. 4, pp. 326—334. © Pleiades Publishing, Ltd., 2016.Original Russian Text © A.T. Mar’yanovich, 2016, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2016, Vol. 52, No. 4, pp. 292—298.PROBLEM PAPERSBlood–Brain Barrier and Evolution of Peptide Regulation of Physiological FunctionsA. T. Mar’yanovichMechnikov North-West State Medical University, St. Petersburg, Russiae-mail: atm52@mail.ruReceived February 25, 2016Abstract—Literature and own data on central effects of regulatory peptides (155 substances from 32 families) have been analyzed. Peptides produced by peripheral tissues affect the brain through the almost impermeable for them blood–brain barrier and evoke numerous central effects. The mechanisms of this impact are as follows: peptides bind to specific receptors located on vagal afferent terminals and in the circumventricular organs as well as (to a lesser extent) penetrate into the brain with the aid of specific transport systems or by simple diffusion. The number of these trans-barrier communications depends on the evolutionary age of the regulated physiological function: the more ancient the function is, the greater number of peripheral peptides are involved in such trans-barrier communications.DOI: 10.1134/S0022093016040074Key words: evolution, peptides, food intake, blood pressure, homeothermy.Peptide-regulated physiological functions and the blood–brain barrier: time of formationFor comparative analysis, I have chosen three physiological functions appreciably differing in the time of their emergence during evolution: (a) food intake regulation—as most ancient, (b) maintenance of a relatively constant level of blood (hemolymph) pressure—as a function of the “medium evolutionary age” (for want of any conventional definition, we have to coin the term homeotension), and (c) homeothermy—as one of the youngest functions. I have analyzed a body of literature and my own data on central effects of regulatory peptides (155 substances from 32 fami-lies).Food intake regulation is intrinsic yet to the most primitive extant metazoan, the hydra Hydra vulgaris [2]. Peptides regulate its behavior [3]. In INTRODUCTIONOver the last four decades, hundreds of regula-tory peptides have been isolated, identified and then synthesized in vitro [1]. An obvious contra-diction has arisen between two groups of facts, namely:(a) numerous regulatory peptides, produced in peripheral tissues or introduced to blood flow, evoke diverse central effects;(b) brain parenchyma is separated from blood by the blood–brain barrier (BBB) almost imper-meable for peptides.An attempt to eliminate this contradiction is a major impetus to write this paper. The way to-ward a solution lies, in my opinion, in comparing evolution of peptide-regulated physiological func-tions to evolution of the BBB.