The nature of the receptor mediating stimulant effects of histamine on rapidly adapting vagal afferents in the lungs.

Abstract

The effects of histamine H1- and H2-receptor antagonists were studied on responses of intrapulmonary rapidly adapting receptors to aerosols of histamine to the lungs in dogs. Effects of H1- and H2-agonists on these airway sensory receptors were also examined. Neither i.v. infusion of metiamide (5 mg/kg min for 35 min) in 7 experiments, nor i.v. bolus injection of burimide (15 mg/kg) in 6 experiments, both substances being H2-antagonists, altered the response of rapidly adapting receptors to aerosols of histamine (from 0.1 or 1.0% solutions). Chlorpheniramine (H1-antagonist), 2-5 mg/kg, i.v., completely abolished responses of rapidly adapting receptors to histamine in 7 experiments in which metiamide was given previously and in 7 other preparations in which it had not, but had no effect on responses to prostaglandin F2.alpha.. Chlorpheniramine itself caused a brief stimulation of rapidly adapting receptors. The H2-agonist S-[3-(N,N-dimethylamino)propyl] isothiourea (Dimaprit), given as aerosol (1% solution for 2 min) or i.v. (2 mg/kg), was without effect on activity of 4 airway rapidly adapting receptors. These receptors were stimulated by the H1-agonist 2,(2 pyridylethylamine) dihydrochloride (PEA), administered both as aerosol (from a 10% solution) and i.v. (0.4-2 mg/kg). These stimulant effects were abolished by chlorpheniramine. Stimulation of airway rapidly adapting receptors by histamine may be mediated by histamine H1-receptors.