Pharmacologic evaluation of A23187-induced contractions of three distinct preparations of guinea pig lung parenchymal strips.
The present investigation examined the pharmacologic profiles of three distinct guinea pig lung parenchymal strips (LPS): intact LPS, denuded LPS (devoid of any lung pleura) and pleural surface strips. All three preparations responded similarly to increasing concentrations of KCl, whereas maximum contractile responses of the intact LPS and pleural surface strips to histamine, LTD4 and U46619, a thromboxane A2 mimetic, were significantly greater (P less than 0.001) than those elicited by the denuded LPS. Moreover, concentration-response curves for intact LPS and pleural surface strips to ovalbumin and ionophore A23187 challenges were equivalent to each other, which were significantly (P less than 0.001) higher in magnitude than that for the denuded LPS. The net contractile response of the denuded LPS to A23187 was significantly reduced by 35% in the presence of 1 x 10(-5) M A-64077, a 5-lipoxygenase inhibitor, and nearly abolished with the addition of 1 x 10(-6) M pyrilamine and 4 x 10(-6) M indomethacin. In contrast, the maximum contractile responses of the intact LPS and pleural surface strips were reduced by 40 and 30%, respectively, in the presence of all three inhibitors. On the other hand, morphometric analysis revealed that the density of mast cells in the smooth muscle of lung pleura was as high as that found in the bronchiolar area (2.35 +/- 0.31 vs. 2.62 +/- 0.28 per 0.05 mm2). In contrast, mast cells were scarcely identified in the alveolar parenchyma.(ABSTRACT TRUNCATED AT 250 WORDS)
Wong
W S
WS
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Bendele
A M
AM
Fleisch
J H
JH
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D004347:Drug Interactions; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006918:Hydroxyurea / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D013189:SRS-A / Q000494:pharmacology
D011450:Prostaglandin Endoperoxides, Synthetic; D013189:SRS-A; D000001:Calcimycin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D006632:Histamine; D011738:Pyrilamine; C063449:zileuton; D006918:Hydroxyurea; D007213:Indomethacin