title: Characterizing the site and mode of action of dynorphin at hippocampal mossy fiber synapses in the guinea pig.
abstract: Extracellular field potential recordings from the CA3 region in guinea pig hippocampal slices were used to study the release and action of dynorphin at the mossy fiber synapse. Dynorphin A(1-17) or U69593 inhibited mossy fiber synaptic responses in preparations in which the CA3 region was surgically isolated from the rest of the hippocampus. This inhibition was completely reversed by the kappa 1 selective antagonist nor-BNI, thus establishing the presence of functional kappa 1 receptors in CA3. Inhibitory effects of dynorphin on mossy fiber responses were unaltered in the presence of the N- or P-type Ca2+ channel blockers, omega-CgTx or omega-Aga IVA, respectively. This indicates that the action of dynorphin is independent of the particular type of Ca2+ channel that mediates transmitter release at the mossy fiber terminal. Heterosynaptic inhibition of mossy fiber responses was observed in the presence of nifedipine, omega-CgTx, or omega-Aga IVA, indicating that dynorphin release does not depend specifically on L-, N-, or P-type Ca2+ channels. The blockade of heterosynaptic inhibition by the membrane-permeant Ca2+ chelator EGTA-AM suggests the involvement of a slow Ca(2+)-dependent process in dynorphin release. On the basis of a variety of experimental evidence, we propose that the time course of heterosynaptic inhibition is determined primarily by the time course of clearance of dynorphin in the extracellular space.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California at San Francisco 94143-0450, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Castillo
authors.forename: P A
authors.initials: PA
authors.lastname: Salin
authors.forename: M G
authors.initials: MG
authors.lastname: Weisskopf
authors.forename: R A
authors.initials: RA
authors.lastname: Nicoll
mesh_terms: D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D004399:Dynorphins / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D008959:Models, Neurological; D009412:Nerve Fibers / Q000187:drug effects*; D009433:Neural Inhibition; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D013569:Synapses / Q000187:drug effects*; D013997:Time Factors
chemical_list: D002021:Buffers; D015220:Calcium Channels; D017473:Receptors, Opioid, kappa; D004399:Dynorphins; D002118:Calcium