Regional difference in responsiveness of adenosine-sensitive cyclic AMP-generating systems in chronic epileptic cerebral cortex of the rat.
Cyclic AMP accumulation in brain slices incubated with adenosine or the adenosine analogue 2-chloroadenosine was examined in different areas of rat cerebral cortex following a unilateral injection of FeCl2 solution into the sensorimotor cortex to induce chronic epileptic activity. In the epileptic cortex, cyclic AMP accumulation in cortical slices was elicited three- to 11-fold by adenosine. The elicitation by adenosine of cyclic AMP accumulation was markedly inhibited by the adenosine antagonist 8-phenyltheophylline. In anterior cortical areas of rats in which the appearance of electrographic isolated spikes was dominant either ipsilateral or contralateral to the injection site 8 days or more after the injection, the adenosine-elicited accumulation of cyclic AMP was greater on the side of dominant spike activity than on the other. In anterior cortical areas of rats showing nearly equal spike activity on the two sides 19 days or more after the injection, the cyclic AMP accumulation was greater on the side ipsilateral to the injection site than on the other. In anterior and posterior cortical areas of rats showing spike-and-wave complexes and isolated spikes 1 month or more after the injection, the cyclic AMP accumulation was greater on the ipsilateral side than on the other. Similar regional differences in the adenosine-elicited accumulation of cyclic AMP were detected in the presence of the adenosine uptake inhibitor dipyridamole or the phosphodiesterase inhibitor DL-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 20-1724). The cyclic AMP accumulation was elicited five- to 17-fold by 2-chloroadenosine, in which case the elicitation was markedly inhibited by 8-phenyltheophylline. Regional differences in the 2-chloroadenosine-elicited accumulation of cyclic AMP were similar to those with adenosine and were detected in the presence of Ro 20-1724 or adenosine deaminase. The regional differences which correlated with the electrographic discharge patterns were due mainly to persistent changes in cyclic AMP accumulation on the primary epileptic side. These results suggest that alterations in adenosine-sensitive cyclic AMP generation in the cortex are associated with the neurochemical process leading to chronic iron-induced epilepsy.
Hattori
Y
Y
Department of Physiology, Okayama University Medical School, Japan.
D015762:2-Chloroadenosine / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D000242:Cyclic AMP / Q000378:metabolism*; D004827:Epilepsy / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D011983:Receptors, Purinergic; D015762:2-Chloroadenosine; D013806:Theophylline; D000242:Cyclic AMP; C028322:8-phenyltheophylline; D000243:Adenosine Deaminase; D000241:Adenosine