Molecular mechanisms of the regulatory effect of biogenic amines on the functional activity of the adenylate cyclase signal system in nerve ganglia of the mollusk Anodonta cygnea

Abstract

Hormone-sensitive adenylate cyclase signal system (ACSS) consisting of three major components-a receptor, a heterotrimeric G protein, and an adenylatecyclase system fragment-plays a key role in implementation of the regulatory effect of a broad spectrum of hormones and neurotransmitters of cells of vertebrates and invertebrates. Studying the molecular mechanisms of action of these regulatory molecules on the functional activity of adenylate cyclase is one of the key problems in biochemistry and molecular endocrinology, which is of great theoretical and practical importance for medicine and pharmacology. In the past years, a considerable success was achieved in studying the ACSS in the nervous system of vertebrates, and a relationship between disturbance in its functioning and development of a number of diseases of the human and animals was established. However, the ACSS in nervous tissue of invertebrates has been studied much less extensively [1]. To this end, it should be mentioned that studying the ACSS in nervous tissue of invertebrates is necessary for understanding the pathways whereby the sensitivity of nervous tissue to hormones is formed and the molecular mechanisms underlying their regulatory effect on neural cells.The goal of this study was to perform a comparative study of the effect of biogenic amines (octopamine, dopamine, serotonin, and noradrenalin) on the functional activity of ACSS components (G proteins and adenylate cyclase) in nerve ganglia of the fresh-water bivalve Anodonta cygnea , as well as to study the molecular mechanisms of their action using antagonists of receptors of biogenic amines and the synthetic peptides 385-394 and 346-355, representing the C-terminal segments of α -subunits of G proteins of the stimulatory (G s ) and inhibitory (G i 2 ) types, respectively.This was the first study to demonstrate that biogenic amines stimulate the activity of adenylate cyclase and the GTP-binding activity of G proteins in the nerve ganglia of the mollusk A. cygnea in a concentrationdependent manner, with their effectiveness decreasing in the following order: octopamine > dopamine > serotonin > noradrenalin. The effect of biogenic amines on adenylate cyclase was potentiated by guanine nucleotides. It is shown that the effect of biogenic amines on ACSS is implemented via different types of heterotrimeric G proteins: G s proteins in the case of octopamine and dopamine and both G s and G i proteins in the case of serotonin and noradrenalin. The antagonists of α 2 -adrenergic, dopamine, and serotonin receptors decrease the stimulatory effect of octopamine on molluscan ACSS, sometimes even more effectively than the corresponding agonists. Thus, we obtained new convincing evidence showing that the main molecular mechanisms underlying the regulatory effect of hormones and neurotransmitters on ACSS in nervous tissue of higher vertebrates have already been formed in bivalve mollusks, representatives of invertebrate animals. On the basis of the results obtained in this study, it can be assumed that these...