title: An investigation into the effect of the type IV phosphodiesterase inhibitor rolipram in the modulation of glutamate release from rat prefrontocortical nerve terminals.
abstract: The present study was conducted to explore the influence of rolipram, a specific inhibitor of the phosphodiesterase type 4 (PDE4) isoform, on glutamate release in the rat prefrontal cortex, using isolated nerve terminal (synaptosome) preparation. In prefrontocortical nerve terminals, rolipram potentiated the Ca(2+)-dependent release of glutamate evoked by 4-aminopyridine (4AP) in a concentration-dependent manner. This potentiation of release was occluded by the activation of PKA by Sp-cAMP or beta-adrenergic receptor agonist and prevented by the inhibition of PKA by Rp-cAMP or KT5720, indicating a PKA-mediated mechanism. The rolipram-mediated potentiation of glutamate release is associated with an increase both in the 4AP-evoked depolarization of the synaptosomal plasma membrane potential and in 4AP-evoked Ca(2+) influx into synaptosomes. Moreover, Ca(2+) ionophore ionomycin-induced glutamate release was also facilitated by rolipram. These results concluded that phosphodiesterase 4 inhibited by rolipram produces an increase in PKA activation, which subsequently enhances the voltage-dependent Ca(2+) influx by increasing terminal excitability as well as the vesicular release machinery to cause an increase in evoked glutamate release from rat prefrontocortical nerve terminals.
authors.affiliation: School of Medicine, Fu Jen Catholic University, Hsin-Chuang, Taipei Hsien, Republic of China. med0003@mails.fju.edu.tw
authors.forename: Su-Jane
authors.initials: SJ
authors.lastname: Wang
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000166:cytology*; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D020960:omega-Conotoxins / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D010726:Phosphodiesterase Inhibitors; D026902:Potassium Channel Blockers; D047428:Protein Kinase Inhibitors; D013873:Thionucleotides; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; C016957:adenosine-3',5'-cyclic phosphorothioate; D018698:Glutamic Acid; D011189:Potassium Chloride; D015761:4-Aminopyridine; D000242:Cyclic AMP; D020889:Rolipram; D002118:Calcium