Histamine Induces a Gene-specific Synthesis Secretogranin

The effect of histamine on steady-state mRNA levels of three soluble secretory proteins from chromaffin granules was investigated in cultured bovine adrenal medullary cells. Histamine stimulated secretogranin I1 mRNA 4-fold, with no or only slight effects on chromogranin A and B transcription. After an initial lag phase, secretogranin I1 mRNA increased markedly between 4 and 12 h followed by a plateau phase up to 48 h. The effect of histamine on secretogranin I1 geneexpression was abolished by the H1 receptor antagonist promethazine but not by the Hz blocker cimetidine. The histamine-induced elevation of secretogranin I1 mRNA was partially reduced by the L-type calcium channel blocker nifedipine, indicating a contribution of extracellular calcium in the second messenger signaling pathway involved. At present, the H1 histaminergic receptor is the first membrane receptor found regulating secretogranin I1 biosynthesis in chromaffin cells. The selective up-regulation of secretogranin I1 mRNA but not of chromogranin A and B by histamine is another example illustrating that the synthesis regulation of secretory components co-stored in large vesicles of neuroendocrine cells is pecific to the individual gene. Together with results obtained earlier, our data demonstrate a marked variation in the relative composition of peptides secreted from adrenal medulla into circulation following different physiologic conditions.