Direct measurement of mRNA levels can be made using cDNA probes and one can derive an estimate of peptide turnover by measuring the precursor mRNA, the precursor and the peptide itself. Treatment of bovine adrenal chromaffin cells with 8-Br-cyclic AMP results in an increase of both proenkephalin (PE) and tyrosine hydroxylase (TH) mRNA in these cells, which is time- and dose-dependent and not replicated by 8-Br-cyclic GMP. There is a comparable change in the content of enkaphalin-like peptides. Dexamethasone increases only PE mRNA and enkephalin peptides while reserpine depletes catecholamines and leads to TH induction while depleting PE mRNA and total enkephalin peptides. Depolarization by veratridine depletes enkephalins and catecholamines rapidly. PE mRNA has increased 24 hr later, a response which is enhanced by dexamethasone, whereas TH mRNA has not changed even by 48 hr. Use of cDNA probes for PE and for proopiomelanocortin (POMC) has shown a differential distribution of the mRNAs in the CNS as well as differential regulation by such chronic drug treatments as haloperidol, reserpine, fenfluramine or 5,7-dihydroxytryptamine. Certain drugs alter peptide content by increasing biosynthesis of the mRNA whereas others act at the level of utilization.
