Histamine induces a gene-specific synthesis regulation of secretogranin II but not of chromogranin A and B in chromaffin cells in a calcium-dependent manner.

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 II mRNA 4-fold, with no or only slight effects on chromogranin A and B transcription. After an initial lag phase, secretogranin II mRNA increased markedly between 4 and 12 h followed by a plateau phase up to 48 h. The effect of histamine on secretogranin II gene-expression was abolished by the H1 receptor antagonist promethazine but not by the H2 blocker cimetidine. The histamine-induced elevation of secretogranin II 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 II biosynthesis in chromaffin cells. The selective up-regulation of secretogranin II 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 specific 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.