Enhancement of NMDA receptor-mediated synaptic potential by isoproterenol is blocked by Rp-adenosine 3',5'-cyclic monophosphothioate.
The intracellular mechanisms underlying the facilitatory action of isoproterenol (Iso) on the NMDA receptor-mediated synaptic potential (EPSPNMDA) was investigated in an in vitro slice preparation of rat amygdala. Intracellular recordings were made from basolateral amygdala neurons in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) and picrotoxin (50 microM) which block non-NMDA and GABAA receptors, respectively. Superfusion of Iso (15 microM) produced a sustained increase in EPSPNMDA. Rp-adenosine-3',5'-cyclic monophosphotioate (Rp-cAMPS), a potent inhibitor of protein kinase A (PKA) alone decreased the amplitude of EPSPNMDA below baseline values and prevented the subsequent potentiation by Iso. Forskolin, a direct activator of adenylate cyclase, mimics the effect of Iso, and Rp-cAMPS also reversed forskolin-induced enhancement of EPSNMDA. These results suggest that cAMP-dependent protein kinase mediates the enhancement of EPSPNMDA by Iso in the amygdala.
Huang
C C
CC
Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan City, Taiwan, ROC.
Tsai
J J
JJ
Gean
P W
PW
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010852:Picrotoxin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*; D013873:Thionucleotides / Q000494:pharmacology*
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D005576:Colforsin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol; D010852:Picrotoxin; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate