Release of cholecystokinin from rat cerebral cortex in vivo: role of GABA and glutamate receptor systems.
Using cortical cups in chloralose-urethanized rats, the in vivo release of cholecystokinin-like immunoreactivity (CCK-LI) from cerebral cortex was examined. Resting levels of cholecystokinin-like immunoreactivity ranged from 20 to 30 pg/20 min sample. The addition of potassium (40 mM) in excess, resulted in a highly significant elevation in the levels of CCK-LI in the cortical superfusate. Deletion of calcium and the substitution of cobalt (10 mM), resulted in a significant reduction in both resting release and the release otherwise evoked by the addition of potassium. Focal electrical stimulation of the cortex (20 Hz), resulted in a significant (1.9 +/- 0.2-fold, n = 8) increase in the levels of CCK-LI. The addition of glutamate (10(-6)-10(-4) M) of kainic acid (10(-8)-10(-6) M), also resulted in significant elevations in the levels of CCK-LI. The co-administration of a putative glutamate receptor antagonist, kynurenic acid (10(-4) M) resulted in a significant reduction in the levels of release otherwise evoked by the addition of glutamate, but not by electrical stimulation. The addition of GABA (10(-5)-10(-3) M) resulted in a dose-dependent decrease in the resting release of CCK-LI, and the release evoked by glutamate. Picrotoxin (10(-6)-10(-4) M), resulted in a highly significant increase in the levels of CCK-LI in the cortical effluent. These results are consistent with a tonic GABAergic inhibition of CCK-releasing neurons. The treatment of the animal with diazepam (30 mg/kg, i.p.) also resulted in a significant reduction in resting release and the release otherwise evoked by focal cortical stimulation.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism*; D002766:Cholecystokinin / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D008297:Male; D010852:Picrotoxin / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000502:physiology*; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D000596:Amino Acids; D002118:Calcium; D002766:Cholecystokinin; D003975:Diazepam; D010852:Picrotoxin; D011188:Potassium; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D013779:Tetrodotoxin