Presynaptic histamine H1- and H3-receptors modulate sympathetic neurotransmission in isolated guinea pig vas deferens.

The action of (R)-alpha-methylhistamine (alpha-MeHA), a selective H3-receptor agonist, on field stimulation induced contraction of guinea pig vas deferens was composed of 2 components: the "inhibition" (0.1-100 nmon.L-1) and the "enhancement" (1-10 mumol.L-1). In the presence of histamine H1 antagonist, chlorpheniramine (1 mumol.L-1), alpha-MeHA (0.1 nmol.L-1-10 mumol.L-1) showed only a concentration-dependent inhibition. Selective histamine H3-receptor antagonist, thioperamide (1 nmol.L-1-10 mumol.L-1) antagonized the inhibitory effect of alpha-MeHA and increased the contractile amplitude of vas deferens elicited by field pulses when thioperamide was used alone. alpha-MeHA 10 mumol.L-1 enhanced the contractile amplitude, which was reversed by chlorpheniramine 1 mumol.L-1, but not by ranitidine (1 mumol.L-1). Pyridelethylamine, an H1-receptor agonist, facilitated concentration-dependently the contractile response of vas deferens. The effect was antagonized by chlorpheniramine, but not by ranitidine. Dimaprit, an H2-receptor agonist had no effect on the field stimulation induced sympathetic response. Both alpha-MeHA and pyridelethylamine failed to influence the contraction of vas deferens elicited by direct field stimulation in smooth muscle or by exogenously applied norepinephrine. It was concluded that histamine H1- and H3-receptors existed in sympathetic terminals of guinea pig vas deferens and facilitated or inhibited the sympathetic neurotransmission.