Involvement of adenosine-sensitive cyclic AMP-generating systems in cobalt-induced epileptic activity in the rat.
An injection of cobalt chloride solution into the unilateral sensorimotor cortex of rats induced electrographic epileptic activity, which was followed by a peripheral motor disturbance. Brain slices were prepared from the cortical region including the injection site and from the other cortical regions of rats between 8 and 50 days after the injection. In the cortical slices, we examined cyclic AMP accumulations elicited by adenosine and its stable analogue 2-chloroadenosine. Adenosine and 2-chloroadenosine at their maximal dose increased cyclic AMP accumulation six- to 10-fold and 10-15-fold, respectively, and the elicitation was markedly inhibited by the adenosine antagonist 8-phenyltheophylline. The cyclic AMP accumulation was increased in the primary epileptic region of the cortex adjacent to the injection site of cobalt chloride solution, whereas it was unchanged in the other cortical regions. The increase in cyclic AMP accumulation was observed regardless of the presence or absence of the adenosine uptake inhibitor dipyridamole, the phosphodiesterase inhibitor DL-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone, and adenosine deaminase. Such an increased accumulation of cyclic AMP in the primary epileptic cortex was detected as early as 8 days after the injection. The cyclic AMP accumulation continued to increase and reached a peak level 17-19 days after the injection, and it returned to the control levels after 40-50 days, in correspondence with the electrographic and behavioral findings. It is concluded that alterations in adenosine receptor-mediated generation of cyclic AMP in the primary epileptic cortex are closely associated with the central process of cobalt-induced epilepsy.(ABSTRACT TRUNCATED AT 250 WORDS)
Hattori
Y
Y
Department of Physiology, Okayama University Medical School, Japan.
Moriwaki
A
A
Hayashi
Y
Y
Hori
Y
Y
D015762:2-Chloroadenosine / Q000494:pharmacology*; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000241:Adenosine / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D003035:Cobalt / Q000008:administration & dosage / Q000633:toxicity*; D000242:Cyclic AMP / Q000378:metabolism*; D004569:Electroencephalography / Q000187:drug effects; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology
D015762:2-Chloroadenosine; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D003035:Cobalt; D013806:Theophylline; D000242:Cyclic AMP; C028322:8-phenyltheophylline; C018021:cobaltous chloride; D000241:Adenosine