title: Genetic control of indirect airway responsiveness in the rat.
abstract: Many of the airway responses to endogenous and exogenous stimuli are caused by indirect mechanisms such as the activation of neurons and/or inflammatory cells. In the present study we compare the bronchoconstrictor and the plasma protein extravasation response to adenosine and tachykinins in two highly inbred rat strains, F344 and BDE. BDE-rats have a bronchoconstrictor response to adenosine at lower doses. Challenge with the A3-adenosine receptor agonist APNEA demonstrates that the difference in airway responsiveness to adenosine between BDE- and F344-rats is probably related to a higher number of A3-receptors on the airway mast cells of BDE-rats. In contrast, F344-rats have a higher airway responsiveness to tachykinins than BDE-rats. Tachykinins cause bronchoconstriction in F344-rats mainly by an indirect mechanism, involving stimulation of NK1-receptors and mast cell activation. In BDE-rats they cause bronchoconstriction by a direct effect on airway smooth muscle via activation of NK2-receptors. Finally we also observed a difference between F344- and BDE-rats with regard to the mechanisms involved in the plasma protein extravasation in the airways caused by substance P or capsaicin. In F344-rats but not in BDE-rats mast cell activation and the release of 5-hydroxytryptamine is partly responsible for this plasma protein extravasation.
authors.affiliation: Department of Respiratory Diseases, University Hospital, Ghent, Belgium.
authors.forename: R A
authors.initials: RA
authors.lastname: Pauwels
authors.forename: P R
authors.initials: PR
authors.lastname: Germonpré
authors.forename: J C
authors.initials: JC
authors.lastname: Kips
authors.forename: G F
authors.initials: GF
authors.lastname: Joos
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000235:genetics*; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D017835:Nedocromil / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D018039:Receptors, Tachykinin / Q000187:drug effects / Q000502:physiology; D012129:Respiratory Function Tests; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology
chemical_list: D001798:Blood Proteins; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D018039:Receptors, Tachykinin; D012702:Serotonin Antagonists; D015320:Tachykinins; D017835:Nedocromil; D012701:Serotonin; D013373:Substance P; D001285:Atropine; D000241:Adenosine; D002211:Capsaicin; D008784:Methysergide