PHARMACOLOGICAL EVALUATION OF A23187-INDUCED CONTRACTIONS OF 3 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 < 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 < 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. Our data suggest that: 1) the contractile responses of intact LPS correlate best with that of the pleural surface strips, indicating that the lung pleura is a major contributor to the net contraction of guinea pig LPS; and 2) since intact LPS and pleural surface strips were relatively resistant to pharmacologic inhibition by all three blockers as compared to the denuded LPS, there might be qualitative and/or quantitative differences in arachidonic acid metabolism and mediators released from each compartment of the guinea pig lung to A23187 challenge.