Modulation by alpha 2-adrenergic stimulation of IgE-mediated 14C-serotonin release from rat mast cells.

The formaldehyde method was used to examine the effects of clonidine and methoxamine on IgE-mediated 14C-serotonin release from rat mast cells in vitro. Clonidine (10(-11) -10(-8) M) caused dose-related enhancement of the mediator release 7 min after the antigen challenge; yohimbine (10(-6) M) blocked this enhancement by clonidine (10(-6) M), but prazosin (10(-6) M) did not. Methoxamine did not enhance this immunological release reaction at concentrations up to 10(-6) M. PGE1 (2 X 10(-8) -2 X 10(-5) M), isoproterenol (10(-10) -10(-8) M), dopamine (4 X 10(-8) -4 X 10(-8) M) and aminophylline (6 X 10(-6) -6 X 10(-4) M) caused dose-related inhibition of this mediator release 1 min after antigen challenge. Clonidine (10(-13) -10(-12) M), but not methoxamine (10(-8) -10(-6) M), reversed dose-dependently this inhibition of mast cells by PGE1 (2 X 10(-6) M), isoproterenol (10(-8) M), dopamine (4 X 10(-6) M); yohimbine (10(-8) M) antagonized this reversing action of clonidine (10(-12) M), but prazosin (10(-10) M) did not. Neither clonidine (10(-14) -10(-11) M) nor methoxamine (10(-8) -10(-6) M) reversed the inhibitory action of aminophylline (2 X 10(-4) M). These results suggests that clonidine enhances IgE-mediated 14C-serotonin release from rat mast cells and also antagonizes the inhibition of mast cells by PGE1, isoproterenol and dopamine, but not by aminophylline in this immunological reaction through alpha 2-adrenergic receptors, and that the inhibition of adenylate cyclase of mast cells is one of the biochemical actions of alpha 2-adrenergic mechanisms.