LIMBIC SEIZURES INDUCE NEUROPEPTIDE AND CHROMOGRANIN MESSENGER-RNA EXPRESSION IN RAT ADRENAL-MEDULLA

Rats heated with kainic acid develop limbic seizures and have elevated levels of circulating catecholamines resulting from an extensive stim ulation of the adrenal gland. We investigated the levels of several co nstituents of chromaffin granules in rat adrenal medulla after injecti on of kainic acid. This treatment increased mRNA steady-state levels o f enkephalin, neuropeptide Y and chromogranin B 2-6-fold. Elevated lev els of these constituents were found as early as 2 h after treatment a nd lasted up to 24 h. Chromogranin A. and secretogranin II mRNA levels , on the other hand, remained unchanged. Adrenal catecholamine concent rations were reduced by 80%. Pre-treatment of rats with thiopental pri or to kainic acid prevented seizures, the decline in catecholamines an d 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 m RNA may be regulated by a direct effect of kainic acid on chromaffin c ells. The pattern of changes in mRNA expression differed from that see n after insulin hypoglycemia or reserpine treatment. Thus, stimulation of the splanchnic innervation in vivo by various means leads to an in dividual and independent regulation of granule constituents by quite d ifferent mechanisms. (C) 1997 Elsevier Science B.V.