(R)-ALPHA-METHYLHISTAMINE AUGMENTS NEURAL, CHOLINERGIC BRONCHOSPASM IN GUINEA-PIGS BY HISTAMINE-H1 RECEPTOR ACTIVATION

In the airways, activation of histamine H-3-receptors with (R)-alpha-methylhistamine inhibits neurally induced cholinergic contractions in vitro and peptidergic responses in vivo. The role of histamine H-3-receptors on the cholinergic bronchoconstriction induced by electrical stimulation of the dorsal medulla in guinea pigs was assessed in this study. There was no evidence for an H-3-receptor mediated inhibition of cholinergic bronchospasm in vivo. However, there was potentiation of central cholinergic bronchoconstriction by (R)-alpha-methylhistamine or histamine by a mechanism involving H-1-receptors. I.v. (R)-alpha-methylhistamine (0.3-3 mg/kg) or histamine (0.001-0.01 mg/kg) produced a transient bronchospasm and potentiated the bronchoconstriction due to medullary stimulation. These effects of (R)-alpha-methylhistamine and histamine were blocked by the histamine H-1-antagonist, chlorpheniramine (30-mu-g/kg i.v.) but not by H-2- or H-3-receptor antagonists. (R)-alpha-Methyl-histamine did not potentiate the bronchoconstriction due to i.v. methacholine. Other bronchoconstrictor agents such as methacholine and serotonin did not potentiate the CNS-induced bronchospasm.