G.N. Andrianov, A.D. Nozdrachev, I.V. Ryzhova, T.V. Tobias

Defensins are one of the major groups of natural peptide antibiotic peptides that are considered as mediators of innate and adaptive immunity. At the same time, there is good reason to believe that defensins, in addition to their role in integrating the innate and adaptive immune responses, may act on membrane receptors located on the neurons or afferent nerve fibres and thus they can modulate the properties of these receptors and the responsiveness of neuronal elements. The present study was undertaken to determine the role of human defensin NP-1 in the excitability of the peripheral vestibular system in the frog. For this purpose, using multiunit recording of afferent activity of the whole semicircular canal nerve we tested the effects of defensin on resting and chemically-induced activities of nerve fibers innervating the semicircular canals. Bath-applied de-fensin caused a frequency decrease in resting activity, with magnitude of the effect depending on concentration. For most units, the threshold concentration of defensin was 0.1 nM. Combined application of L-glutamate and defensin induced a frequency increase but the responses were considerably smaller as compared to control perfusion of L-glutamate. Firing evoked by the action of L-glutamate agonists - kainic acid (KA),  - amino-3-hydroxy-5- methylisoxazole-4-propioinic acid (AMPA), N-methyl-D-?aspartic acid (NMDA) and (1S, 3R)-1-aminocyclopentane-trans-1, 3-dicarboxilic acid (ACPD) could be inhibited by defensin, suggesting that defensins exert inhibitory control over both ionotropic and metabotropic glutamate receptors. The postsynaptic L-glutamate-induced responses in high Mg2+ solution were highly susceptible to the external perfusion of de-fensin and addition of nanomolar concentrations of defensin drastically inhibited the frequency increase under L-glutamate. This indicates that one possible site for defensin action is on the postsynaptic membrane. The specific opioid receptor antagonist naloxone antagonized the inhibi-tory influence evoked by defensin. Results of this study indicate that defensins may be involved in the interaction with opioid receptors on vestibular hair cells. It is possible to suggest that one site of action of these peptides is the defensin receptor, the activation of which induces an increase in the production of endogenous opioid peptides and stimulation of the opioid receptors. An alterna-tive possibility exists that defensins can act directly through the mechanism of activation of the opioid receptors. The above data have demonstrated the existence of cellular mechanisms by which defensins can control the afferent discharge and modulate the effects of neurotransmitter L-Glu in the vestibular end organs in the frog and on the potential of sensory receptors to participate in the inflammatory response. Our results support the hypothesis on a link between the immune and nervous systems, and on the involvement of sensory receptors in the formation of the inflammatory reaction.