Ca2+-Dependent Histaminergic Regulation of Proenkephalin mRNA Levels in Cultured Adrenal Chromaffin Cells

Abstract

The effect of histamine on messenger ribonucleic acid levels encoding proenkephalin A (mRNAenk) was studied in serum-free cultures of bovine adrenal chromaffin cells. Histamine (10-7-10-4 M) stimulated mRNAenk, with a maximum response (5-fold) at 10-5 M, an effect which could be abolished by the H1 receptor antagonist clemastine (10-7 M) but not by the H2 receptor antagonist cimetidine (10-7-10-5 M). The histamine stimulation was partially reduced by the Ca++ channel blockers D600 (10-5 M) and nifedipine (10-7 M). On the other hand, muscarinic receptor stimulation, which similarly to histamine is known to stimulate phosphoinositide hydrolysis in chromaffin cells, did not alter mRNAenk in these cells. These data show that mRNAenk levels may be modulated by activation of the H1 receptor and that this effect is partially dependent on the activation of voltage-dependent Ca2+ channels.