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

1. The effects of histamine H1- and H2-agonists on these airway sensory receptors were also examined. 2. Neither I.V. infusion of metiamide (5 mg/kg, min for 35 min) in seven experiments, nor I.V. bolus injection of burimamide (15 mg/kg) in six other experiments, both substances being H2-antagonists, altered the response of rapidly adapting receptors to aerosols of histamine (from 0.1 or 1.0% solutions). 3. Chlorpheniramine (H1-antagonist), 2--5 mg/kg, I.V., completely abolished responses of rapidly adapting receptors to histamine in seven experiments in which metiamide had been given previously and in seven 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. 4. 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 four airway rapidly adapting receptors. These receptors were stimulated, however, 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. 5. The results indicate that stimulation of airway rapidly adapting receptors by histamine is mediated by histamine H1-receptors.