Involvement of ionotropic purinergic receptors in the histamine-induced enhancement of the cough reflex sensitivity in guinea pigs.
We examined the effect of inhaled histamine on citric acid-induced coughs and clarified the role of ionotropic purinergic receptors in the resulting changes. Although the inhalation of 0.1 M citric acid by itself produced only a few coughs in guinea pigs, exposure to histamine, at concentrations of 0.3 to 1 mM, for 2 min concentration dependently increased the number of citric acid-induced coughs. This histamine-induced increase in the number of citric acid-induced coughs was dose dependently and significantly reduced when animals were pretreated with fexofenadine, a histamine H1 receptor antagonist. The histamine-induced increase in the number of citric acid-induced coughs was completely reduced when animals were co-pretreated with 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5-triphosphate (TNP-ATP, 50 microM), a P2X receptor antagonist, and reactive blue 2, a P2Y receptor antagonist, for 2 min. Furthermore, the ATP-induced increase in the number of citric acid-induced coughs was dose dependently and significantly decreased when animals were pretreated with fexofenadine, at doses of 0.3, 1 and 3 mg/kg, p.o. These results suggest that histamine enhances the excitability of rapidly adapting receptors to tussive stimuli via modulation of ATP release in the airways. Furthermore, ATP might act not only on P2X receptors to directly activate rapidly adapting receptors, but also on P2Y receptors to increase histamine release, indirectly increasing the cough reflex sensitivity.
Kamei
Junzo
J
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo 142-8501, Japan. kamei@hoshi.ac.jp <kamei@hoshi.ac.jp>
Takahashi
Yoshiki
Y
D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity; D000280:Administration, Inhalation; D000818:Animals; D019343:Citric Acid / Q000008:administration & dosage / Q000633:toxicity; D003371:Cough / Q000139:chemically induced / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006168:Guinea Pigs; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology; D008297:Male; D058919:Purinergic P2 Receptor Antagonists; D011969:Receptors, Histamine H1 / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058469:Receptors, Purinergic P2X; D012018:Reflex / Q000187:drug effects*; D016593:Terfenadine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
D039563:Histamine H1 Antagonists, Non-Sedating; D058919:Purinergic P2 Receptor Antagonists; D011969:Receptors, Histamine H1; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D019343:Citric Acid; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D016593:Terfenadine; D006632:Histamine; D000255:Adenosine Triphosphate; C093230:fexofenadine