Interactions of morphine with PGE₁, isoproterenol, dopamine and aminophylline in rat mast cells; their effect on IgE-mediated¹⁴C-serotonin release

Abstract

The formaldehyde method was used to examine the interactions of morphine with PGE₁, isoproterenol, dopamine and aminophylline in rat mast cells by their effects on IgE-mediated¹⁴C-serotonin release. PGE₁ (2×10⁻⁸−2×10⁻⁵ M), isoproterenol (10⁻¹⁰−10⁻⁸ M), dopamine (4×10⁻⁸−4×10⁻⁶ M) and aminophylline (6×10⁻⁶−6×10⁻⁴ M) caused dose-related inhibition of the mediator release 1 min after an antigen challenge, and propranolol (10⁻⁷ M) blocked the inhibition by isoproterenol (10⁻⁸ M) but not that by dopamine (4×10⁻⁶ M), while haloperidol (4×10⁻⁶ M) blocked that by dopamine (4×10⁻⁶ M) but not that by isoproterenol (10⁻⁸ M). Morphine (3×10⁻⁷−3×10⁻⁵ M) reversed the inhibitory effects of PGE₁ (2×10⁻⁶ M), isoproterenol (10⁻⁸ M) and dopamine (4×10⁻⁶ M) dose-dependently and stereospecifically; naloxone (2×10⁻⁴ M) antagonized these reversing actions of morphine (3×10⁻⁵ M). Morphine (10⁻⁶−10⁻⁴ M) did not reverse the inhibitory action of aminophylline (6×10⁻⁴ M). These results suggest that the inhibitory responses of mast cells to PGE₁, isoproterenol and dopamine but not to aminophylline in immunological mediator release were reversed by morphine through opioid receptors, and that the inhibition of adenylate cyclase in mast cells is one of the biochemical actions of morphine.