Responses of equine trachealis and lung parenchyma to methacholine, histamine, serotonin, prostanoids, and leukotrienes in vitro.
The responses of equine trachealis and lung parenchymal strips to a range of contractile agonists were studied. Equine trachealis responded to methacholine greater than histamine greater than serotonin as shown by the maximal responses but failed to respond to either leukotrienes (LT), prostaglandin F2 alpha, or U-44069. Equine parenchymal strips showed considerable tonal activity and responded to LTD4 congruent to LTC4 greater than U-44069 = LTE4 greater than methacholine congruent to histamine congruent to serotonin greater than prostaglandin F2 alpha as determined through pD2 values. Neither the concentration response curve to LTD4 nor the intrinsic tonal activity of the preparations was modified by pretreatment with either atropine or indomethacin, although the maximal response to LTD4 was reversed by addition of the LTD4 receptor antagonist, MK-571. Thus arachidonic acid metabolites, including LTs, must be considered potential mediators of equine small airway disease, a potential model of human bronchial asthma.
Doucet
M Y
MY
Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, Qué., Canada.
Jones
T R
TR
Ford-Hutchinson
A W
AW
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001285:Atropine / Q000494:pharmacology; D004195:Disease Models, Animal; D006632:Histamine / Q000494:pharmacology*; D006736:Horses; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D015289:Leukotrienes / Q000494:pharmacology*; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects; D008688:Methacholine Compounds / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011453:Prostaglandins / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology*; D014132:Trachea / Q000033:anatomy & histology / Q000187:drug effects
D015289:Leukotrienes; D008688:Methacholine Compounds; D011453:Prostaglandins; D012701:Serotonin; D001285:Atropine; D006632:Histamine; D007213:Indomethacin