Modulation by adenine nucleotides of epileptiform activity in the CA3 region of rat hippocampal slices.
1. Hippocampal slices (450 microm) generate epileptiform bursts of an interictal nature when perfused with a zero magnesium medium containing 4-aminopyridine (50 microM). The effect of adenine nucleotides on this activity was investigated. 2. ATP and adenosine depressed this epileptiform activity in a concentration-dependent manner, with both purines being equipotent at concentrations above 10 microM. 3. Adenosine deaminase 0.2 u ml(-1), a concentration that annuls the effect of adenosine (50 microM), did not significantly alter the depression of activity caused by ATP (50 microM). 4. 8-Cyclopentyl-1,3-dimethylxanthine (CPT), an A1 receptor antagonist, enhanced the discharge rate significantly and inhibited the depressant effect of both ATP and adenosine such that the net effect of ATP or adenosine plus CPT was excitatory. 5. Several ATP analogues were also tested: alpha, beta-methyleneATP (alpha, beta-meATP), 2-methylthioATP (2-meSATP) and uridine triphosphate (UTP). Only alpha, beta-meATP (10 microM) produced an increase in the frequency of spontaneous activity which suggests a lack of involvement of P2Y or P2U receptors. 6. Suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), P2 receptor antagonists, failed to inhibit the depression produced by ATP (50 microM). The excitatory effect of alpha, beta-meATP (10 microM) was inhibited by suramin (50 microM) and PPADS (5 microM). 7. ATP therefore depresses epileptiform activity in this model in a manner which is not consistent with the activation of known P1 or P2 receptors, suggesting the involvement of a xanthine-sensitive nucleotide receptor. The results are also indicative of an excitatory P2X receptor existing in the hippocampal CA3 region.
Ross
F M
FM
Institute of Biomedical and Life Sciences, University of Glasgow.
Brodie
M J
MJ
Stone
T W
TW
D000227:Adenine Nucleotides / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D000241:Adenosine / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D004827:Epilepsy / Q000201:enzymology / Q000503:physiopathology*; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013498:Suramin / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D000227:Adenine Nucleotides; D010975:Platelet Aggregation Inhibitors; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C053907:8-cyclopentyl-1,3-dimethylxanthine; D011732:Pyridoxal Phosphate; D013498:Suramin; D000255:Adenosine Triphosphate; D013806:Theophylline; D000243:Adenosine Deaminase; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate