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

Abstract

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 H_1-receptor antagonist, clemastine, whereas the H₂-receptor antagonists, ranitidine and cimetidine, were less effective (∼20% inhibition).