title: Inhibition by the chromaffin cell-derived peptide serine-histogranin in the rat's dorsal horn.
abstract: The heptadecapeptide histogranin, synthesized by adrenal chromaffin cells, is implicated in the analgesia produced by transplanting chromaffin cells into the spinal cord, including block of hyperalgesia mediated by NMDA-subtype glutamate receptors. To examine the neurophysiological basis for this analgesia, we applied the stable analog [Ser(1)]-histogranin (SHG) by iontophoresis near extracellularly recorded wide-dynamic range (WDR) neurons in anesthetized rats. When SHG was applied during peripheral electrical stimulation of A and C fibers at 0.1Hz, the C-fiber response was significantly inhibited but the A-fiber response was unaffected. SHG also opposed the NMDA-receptor-dependent post-tetanic facilitation (wind-up) of C-fiber responses produced by increasing the rate of peripheral afferent stimulation to 1Hz for 20s. To test whether block of NMDA-subtype receptors could be wholly or partially responsible for this suppression, SHG was applied during sequential pulsed iontophoresis of three agonists targeting distinct excitatory synaptic receptors: NMDA, kainate and substance P. All three excitatory effects were reversed by SHG; this reversal outlasted the 10-30min observation period when higher SHG doses were applied (>60nA). Histogranin therefore probably produces prolonged spinal analgesia by opposing the basal and potentiating synaptic effects of C-fibers on dorsal horn neurons. Actions besides or in addition to NMDA-receptor antagonism (e.g., agonism at inhibitory postsynaptic receptors or block of voltage-gated cation channels on C-fibers) are implied by the diversity of excitatory transmitters opposed by SHG.
authors: The Miami Project to Cure Paralysis, University of Miami, Miller School of Medicine, R-48, Miami, FL 33136, United States. i.hentall@miami.edu
authors: Ian D
authors: ID
authors: Hentall
authors: Walter A
authors: WA
authors: Hargraves
authors: Jacqueline
authors: J
authors: Sagen
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D009433:Neural Inhibition / Q000187:drug effects*; D020671:Posterior Horn Cells / Q000187:drug effects*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology; D013997:Time Factors
chemical_list: D018690:Excitatory Amino Acid Agonists; D018846:Excitatory Amino Acids; D011506:Proteins; C082312:histogranin