Limbic seizures induce neuropeptide and chromogranin mRNA expression in rat adrenal medulla

Rats treated with kainic acid develop limbic seizures and have elevated levels of circulating catecholamines resulting from an extensive stimulation of the adrenal gland. We investigated the levels of several constituents of chromaffin granules in rat adrenal medulla after injection of kainic acid. This treatment increased mRNA steady-state levels of enkephalin, neuropeptide Y and chromogranin B 2-6-fold. Elevated levels of these constituents were found as early as 2 h after treatment and lasted up to 24 h. Chromogranin A and secretogranin II mRNA levels, on the other hand, remained unchanged. Adrenal catecholamine concentrations were reduced by 80%. Pre-treatment of rats with thiopental prior to kainic acid prevented seizures, the decline in catecholamines and the elevation of enkephalin and neuropeptide Y mRNAs but not that of chromogranin B. On the other hand, the peripherally acting ganglionic blocker chlorisondamine did not protect from the kainic acid-induced up-regulation of chromogranin B mRNA, suggesting that chromogranin B mRNA may be regulated by a direct effect of kainic acid on chromaffin cells. The pattern of changes in mRNA expression differed from that seen after insulin hypoglycemia or reserpine treatment. Thus, stimulation of the splanchnic innervation in vivo by various means leads to an individual and independent regulation of granule constituents by quite different mechanisms.