Histamine activates proenkephalin A mRNA but not phenylethanolamine N-methyltransferase mRNA expression in cultured bovine adrenal chromaffin cells

Abstract

The effects of histamine on the regulation of proenkephalin A (ProEnk A) and phenylethanolamine N-methyltransferase (PNMT) mRNA expression were examined in cultures of bovine adrenal chromaffin cells. Prolonged incubation with histamine resulted in a concentration-dependent increase in the levels of ProEnk A mRNA with little effect on the levels of PNMT mRNA. The activation of ProENK A mRNA by histamine followed a slow time course, reaching 2–3 fold basal levels after 48 h incubation. This activation was antagonized by the H 1-antagonist mepyramine but not by the H 2-antagonist cimetidine indicating involvement of H 1-histamine receptors. The histamine-induced activation of ProEnK mRNA was blocked by the RNA synthesis inhibitor actinomycin D, suggesting that the novo synthesis of ProEnkA mRNA is a requirement for activation. In the presence of the calcium channel blocker D600, the histamine-induced increase in ProEnk A mRNA was greatly reduced, though not abolished. Prolonged incubation with histamine also caused a substantial release of catecholamines and opioid peptides from these cells. These results suggest that the synthesis and release of opioid peptides is controlled by histamine via H 1-receptors. The differential effects of histamine on ProEnk A mRNA and PNMT mRNA expression suggest that different regulatory mechanisms are called upon to regulate the synthesis of opioid peptides and adrenaline in response to stimulation of the chromaffin cells.