Dynorphin-induced depression of the dorsal root potential in rat spinal cord: a possible mechanism for potentiation of the C-fiber reflex.
Dynorphin A (1-13) acetate salt was applied to the exposed spinal cord of rats during electrophysiological recording of the dorsal root potential (DRP) and the DR III arising from dorsal root stimulation. Simultaneously, ventral root potentials indicative of monosynaptic and polysynaptic myelinated pathways were recorded. Amplitudes of the DRP and DR III were decreased for 30 to 60 min in a dose-dependent manner after dynorphin administration with ED50 values of 21 and 28 nmol, respectively. Amplitude of ventral root potentials was also decreased with a maximal effect at 5 min postdrug treatment. In contrast, we (Caudle and Isaac, J. Pharmacol. Exp. Ther. 246: 508-513, 1988b) showed that the polysynaptic unmyelinated pathway (C-fibers) was greatly enhanced by dynorphin treatment and that this pathway was the locus of excitotoxicity (Caudle and Isaac, Brain Res. 443: 329-332, 1988a). Because the DRP reflects gamma-aminobutyric acid-mediated presynaptic inhibition of primary afferent terminals, these data indicate that dynorphin suppresses gamma-aminobutyric acid-mediated inhibition thereby disinhibiting primary afferent transmission. This presynaptic disinhibition may be the mechanism for the selective potentiation of the C-fiber pathway which may account for the selective neuron toxicity, i.e., loss of the C-fiber pathway and sparing of the monosynaptic and polysynaptic myelinated pathways after dynorphin administration.
Department of Pharmacology, University of Illinois College of Medicine, Chicago.
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Stewart
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Isaac
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013126:Spinal Nerve Roots / Q000187:drug effects* / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D005680:gamma-Aminobutyric Acid; D004399:Dynorphins