Neurochemical regulation of cough response to capsaicin in guinea-pigs

Although monumental efforts have been made to define the action sites of cough, the importance of neurotransmitter systems in the cough reflex has received limited attention. We studied the roles for four major neurotransmitters [acetylcholine, histamine, serotonin (5-hydroxytryptamine, 5-HT) and dopamine] in the modulation of the cough reflex. Atropine (muscarinic cholinergic blocking agent), pyrilamine maleate (PM, histamine H₁ blocker), cimetidine (histamine H₂ blocker), 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OHDPAT, specific 5-HT_1A receptor agonist) and SCH-23390 (selective dopamine D₁ receptor antagonist) were examined on the cough response to inhaled capsaicin in conscious guinea-pigs. All the drugs significantly decreased the number of capsaicin-induced coughs in a dose-dependent manner. To compare the sensitivity of these drugs on cough response, we calculated the effective doses for 50% inhibition of cough (ED₅₀₎ when the animals were exposed to 3 × 10^-4 M capsaicin. The ED₅₀ values were 0.03 μM kg^-1 for atropine, 0.2 μM kg^-1 for 8-OHDPAT, 6.2 μM kg^-1 for SCH-23390, 8.5 μM kg^-1 for PM and 13.9 μM kg^-1 for cimetidine. These findings indicated that all these four neurotransmitters may be involved in the regulation of the cough reflex. Multiple changes of these neurotransmitters in disorders of the central nervous system might synergically affect the cough reflex.