Histamine Affects Release and Biosynthesis of Opioid Peptides Primarily via H1‐Receptors in Bovine Chromaffin Cells

Histamine is a potent secretagogue for opioid pentapeptides (Met‐ and Leu‐enkephalin) in adrenal chromaffin cells in vitro. This effect is dependent on extracellular Ca2+ and is reduced by Ca2+ channel blockers such as Co2+, D 600, and nifedipine. Moreover, histamine also produced a profound compensatory increase in cellular peptide content after 48 h of exposure, most likely caused by a four‐ to fivefold increase in the mRNA levels coding for the proenkephalin A precursor. All the histamine‐in‐duced effects (acute release, changes in peptide cell content, proenkephalin A mRNA levels) are antagonized by the H1‐receptor antagonist, clemastine, whereas the H2‐receptor antagonists, ranitidine and cimetidine, were less effective (∼20% inhibition).