title: The role of defensins in the excitability of the peripheral vestibular system in the frog: evidence for the presence of communication between the immune and nervous systems.
abstract: Defensins are one of the major groups of endogenous peptides that are considered to be important antibiotic-like effectors of host innate and adaptive antimicrobial immunity. The current study investigated the electrophysiological effects of externally applied human and rabbit defensins (HNP-1 and RNP-1, correspondingly) on afferent neurotransmission in the frog semicircular canals (SCC). Application of HNP-1 and RNP-1 induces a concentration-dependent decrease in resting activity. Threshold concentrations for both substances were of the order of 0.0001 nM. The firing evoked by L-glutamate (L-Glu) and its agonists alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), kainate and N-methyl-D-aspartate (NMDA) and (1S, 3R)-1-aminocyclopentane-trans-1,3-dicarboxilic acid (ACPD) could be inhibited by HNP-1, suggesting that defensins exert inhibitory control over both ionotropic and metabotropic glutamate receptors. HNP-1 considerably inhibited the L-glutamate/high Mg2+ -induced increase in frequency, thus, demonstrating its postsynaptic site of action. Acetylcholine (ACh) responses under HNP-1 did not differ from the frequency increase induced by ACh alone, and the ACh antagonist atropine left the response to HNP-1 intact. The specific opioid receptor antagonist naloxone (Nal) antagonized the inhibitory response evoked by HNP-1. The results obtained support the evidence for the recruitment of defensins in communication between the immune and nervous systems, and on the potential of sensory receptors to participate in the inflammatory response.
authors.affiliation: Laboratory of Physiology of Reception, Pavlov Institute of Physiology, Russian Academy of Sciences, Nab. Makarova 6, St. Petersburg 199034, Russia. andryu@infran.ru
authors.forename: G N
authors.initials: GN
authors.lastname: Andrianov
authors.forename: A D
authors.initials: AD
authors.lastname: Nozdrachev
authors.forename: I V
authors.initials: IV
authors.lastname: Ryzhova
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000200:Action Potentials; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D023082:Defensins / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D015213:Neuroimmunomodulation; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D011896:Rana temporaria; D011950:Receptors, Cholinergic / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism; D012665:Semicircular Canals / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D009435:Synaptic Transmission; D014722:Vestibule, Labyrinth / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D023084:alpha-Defensins / Q000378:metabolism
chemical_list: D018680:Cholinergic Antagonists; D023082:Defensins; D009292:Narcotic Antagonists; D011950:Receptors, Cholinergic; D017470:Receptors, Glutamate; D011957:Receptors, Opioid; D023084:alpha-Defensins; C406564:defensin NP-1; C406413:human neutrophil peptide 1; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D009270:Naloxone; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D001285:Atropine; D000109:Acetylcholine; D007608:Kainic Acid