Cellular action of cholecystokinin-8S-mediated excitatory effects in the rat periaqueductal gray.
The peptide cholecystokinin (CCK) is one of the major neurotransmitters modulating satiety, nociception, and anxiety behavior. Although many behavioral studies showing anti-analgesic and anxiogenic actions of CCK have been reported, less is known about its cellular action in the central nervous system (CNS). Therefore, we examined the action of CCK in rat dorsolateral periaqueductal gray (PAG) neurons using slice preparations and whole-cell patch-clamp recordings. Application of CCK-8S produced an inward current accompanied by increased spontaneous synaptic activities. The CCK-8S-induced inward current (I(CCK)) was recovered after washout and reproduced by multiple exposures. Current-voltage plots revealed that I(CCK) reversed near the equilibrium potential for K(+) ions with a decreased membrane conductance. When several K(+) channel blockers were used, application of CdCl(2), TEA, or apamin significantly reduced I(CCK). I(CCK) was also significantly reduced by the CCK(2) receptor antagonist, L-365,260, while it was not affected by the CCK(1) receptor antagonist, L-364,718. Furthermore, we examined the effects of CCK-8S on miniature excitatory postsynaptic currents (mEPSCs) in order to determine the mechanism of CCK-mediated increase on synaptic activities. We found that CCK-8S increased the frequency of mEPSCs, but had no effect on mEPSC amplitude. This presynaptic effect persisted in the presence of CdCl(2) or Ca(2+)-free bath solution, but was completely abolished by pre-treatment with BAPTA-AM, thapsigargin or L-365,260. Taken together, our results indicate that CCK can excite PAG neurons at both pre- and postsynaptic loci via the activation of CCK(2) receptors. These effects may be important for the effects of CCK on behavior and autonomic function that are mediated via PAG neurons.
Yang
Yu-Mi
YM
Biomedical Research Center, Korea Institute of Science and Technology (KIST), 39-1 Hawholgok-dong Sungbuk-gu, Seoul 136-791, Korea.
Chung
Jun-Mo
JM
Rhim
Hyewhon
H
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D018408:Patch-Clamp Techniques; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000502:physiology; D010671:Phenylurea Compounds / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D019284:Thapsigargin / Q000494:pharmacology
C090019:8-sulfocholecystokinin octapeptide; D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D026902:Potassium Channel Blockers; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; C058121:L 365260; D004533:Egtazic Acid; D019284:Thapsigargin; D012844:Sincalide