title: Cholecystokinin-2 receptors couple to cAMP-protein kinase A to depress excitatory synaptic currents in rat nucleus accumbens in vitro.
abstract: We recently reported that the activation of cholecystokinin-2 receptors depress evoked excitatory postsynaptic currents (EPSCs) in nucleus accumbens (NAc) indirectly through gamma-aminobutyric acid (GABA) acting on gamma-aminobutyric acid-B (GABA(B)) receptors. Here, we determined the second messenger system that couples cholecystokinin-2 receptors to the observed synaptic depression. Using in vitro forebrain slices of rats and whole-cell patch recording, we tested the hypothesis that cholecystokinin-2 receptors are coupled to cAMP and protein kinase A signaling pathway. Cholecystokinin-8S induced inward currents and depressed evoked EPSCs. Forskolin, an activator of adenylyl cyclase and rolipram that is an inhibitor of phosphodiesterase type IV, independently increased EPSC amplitude and blocked the inward current and synaptic depression induced by cholecystokinin-8S. Furthermore, the membrane-permeable cAMP analog, 8-bromo-cAMP, blocked the cholecystokinin-8S effects. H89, a protein kinase A inhibitor, also blocked cholecystokinin-8S effects. However, depression of the evoked EPSC by baclofen, a GABA(B) receptor agonist, was not blocked by H89 or forskolin. These findings indicate that cholecystokinin-2, but not GABA(B), receptors are coupled to the adenylyl cyclase-cAMP-protein kinase A signaling pathway in the NAc to induce inward currents and cause synaptic depression.
authors.affiliation: Department of Applied Therapeutics, Kuwait University, Box 24923, Safat 13110, Kuwait. kombian@hsc.edu.kw
authors.forename: Samuel B
authors.initials: SB
authors.lastname: Kombian
authors.forename: Kethireddy V V
authors.initials: KV
authors.lastname: Ananthalakshmi
authors.forename: Subramanian S
authors.initials: SS
authors.lastname: Parvathy
authors.forename: Wandikayi C
authors.initials: WC
authors.lastname: Matowe
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism* / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043887:Receptor, Cholecystokinin B / Q000819:agonists / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C090019:8-sulfocholecystokinin octapeptide; D043887:Receptor, Cholecystokinin B; D017868:Cyclic AMP-Dependent Protein Kinases; D012844:Sincalide