(R)-alpha-methylhistamine augments neural, cholinergic bronchospasm in guinea pigs by histamine H1 receptor activation.
In the airways, activation of histamine H3-receptors with (R)-alpha-methylhistamine inhibits neurally induced cholinergic contractions in vitro and peptidergic responses in vivo. The role of histamine H3-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 H3-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 H1-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 H1-antagonist, chlorpheniramine (30 micrograms/kg i.v.) but not by H2- or H3-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.
Hey
J A
JA
Schering-Plough Research, Bloomfield, NJ 07003.
del Prado
M
M
Egan
R W
RW
Kreutner
W
W
Chapman
R W
RW
D000818:Animals; D001986:Bronchial Spasm / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D002490:Central Nervous System / Q000502:physiology; D002744:Chlorpheniramine / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D004558:Electric Stimulation; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D008761:Methylhistamines / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000502:physiology; D011968:Receptors, Histamine / Q000502:physiology; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology*; D018100:Receptors, Histamine H3; D009435:Synaptic Transmission / Q000187:drug effects; D014132:Trachea / Q000187:drug effects / Q000294:innervation
D008761:Methylhistamines; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D018100:Receptors, Histamine H3; D002744:Chlorpheniramine; C069357:alpha-methylhistamine; D006632:Histamine