The role of cAMP as a primary and secondary messenger in interactions between micro- and macroorganisms studied in the model of pathology related to immunodeficiency and extensive cell dehydration.

Cholera toxin (CT) and thermolabile toxin of Escherichia coli (HL-toxin) are ubiquitous adenylate cyclase-stimulating agents in eukaryotic cells, because all cells contain adenylate cyclase (AC) and ganglioside G m 1 , a specific receptor for toxins [1, 2]. AC activation stimulates cAMP synthesis within cells resulting in an increase in the intracellular cAMP level. In immunocompetent cells, this leads to inhibition of DNA synthesis, i.e., to immunodepression [3–6]. In enterocytes, absorption of sodium and chlorine ions is inhibited, whereas the excretion of chlorine ions is stimulated, when cAMP production is increased, which results in cell dehydration [1]. In unicellular organisms, the original (more ancient) cAMP function was that of a primary extracellular messenger, an alarm signal in critical situations, such as changes in environment, exhaustion of nutrient substances etc. [7]. In the course of evolution, as the cell structure and functions became increasingly more complex, cAMP was gradually involved into intracellular events as a second messenger. At the current stage of mammalian development, cAMP is present in all biological liquids of macroorganisms both outside and within cells [3, 7]. We performed biological testing of chemical compounds in order to find potential antitoxin preparations (under the supervision of Academician L.A. Piruzjan). At the first stage, we studied the mechanism of interaction between the ubiquitous adenylate cyclase-stimulating agents CT and cholera-like HL-toxin of E. coli with the target cells of macroorganisms, namely, enterocytes (in the model of experimental diarrhea) and immunocompetent cells (human peripheral blood (HPB) lymphocytes). The purpose of these experiments was to determine the role of enterotoxins and cAMP in the etiology and pathogenesis of pathological conditions caused by extensive dehydration of cells and immunodepression [8–11]. In mouse enterocytes, CT and HL-toxin stimulated AC synthesis, which resulted in an increased intracelluPHYSIOLOGY