EFFECT OF PASSIVE SENSITIZATION ON THE MECHANICAL-ACTIVITY OF HUMAN ISOLATED BRONCHIAL SMOOTH-MUSCLE INDUCED BY SUBSTANCE-P, NEUROKININ-A AND VIP

1 The effect of passive sensitization on the mechanical activity of hu man isolated bronchial smooth muscle induced by the following neuropep tides substance P (SP), neurokinin A (NKA) and vasoactive intestinal p eptide (VIP) was studied both in the absence and in the presence of th e neutral endopeptidase (NEP) inhibitor, phosphoramidon. 2 Cumulative concentration-response curves (CCRC) to these neuropeptides were const ructed in human passively sensitized isolated bronchial rings and comp ared to those in paired controls. Passively sensitized human isolated bronchial rings were tissues incubated overnight in serum from asthmat ic patients atopic to Dermatophagoides pteronyssinus and paired contro ls were tissues originating from the same lung specimens but incubated overnight in serum from healthy donors. 3 In the absence of phosphora midon, passive sensitization significantly increased the amplitude of the contractile responses to SP and NKA including that to the maximal concentration given from 50 +/- 5% to 76 +/- 6% (n = 5, P < 0.05) and from 70 +/- 7% to 101 +/- 6% (n = 5, P < 0.05) of the maximal response to acetylcholine, respectively. Passive sensitization significantly s hifted to the left the CCRC for both tachykinins as measured by the ge ometric means dose-ratios which were 8.5 (95% confidence limits (CL): 3.1-13.9) and 7.3 (95% CL: 4.2-10.3) for SP and NKA, respectively. 4 I n the presence of phosphoramidon (10 mum), passive sensitization still increased significantly the amplitude of the contractile responses to SP and NKA including that to the maximal concentration given from 74 +/- 4% to 11 5 +/- 7% (n = 5, P < 0.05) and from 104 +/- 9% to 146 +/- 16% (n = 5, P < 0.05) of the maximal response to acetylcholine, respe ctively. Passive sensitization still significantly shifted to the left the CCRC for both tachykinins as measured by the dose-ratios which we re 9.0 (95% CL: 4.3-13.6) and 5.4 (95% CL: 2.9-7.9) for SP and NKA, re spectively. 5 The relaxant response to the maximal concentration of VI P given in tissues precontracted with histamine (0.5 mm) was significa ntly reduced by passive sensitization from 41 +/- 4% to 25 +/- 3% (n = 5, P < 0.05) of the amplitude of the precontraction in the absence of phosphoramidon and from 72 +/- 1% to 49 +/- 4% (n = 5, P<0.05) in the presence of phosphoramidon (10 mum). Passive sensitization significan tly shifted to the right the CCRC for VIP as measured by the dose-rati os which were 10.4 (95% CL: 6.6-14.1) and 6.4 (95% CL: 3.0-9.8) in the absence and in the presence of phosphoramidon, respectively. 6 We con clude that passive sensitization enhances the mechanical response to n europeptides which contract human isolated bronchial smooth muscle and reduces that to a neuropeptide which relaxes it. The mechanism of pas sive sensitization-induced changes in the mechanical activity appears to be independent of a decrease in NEP activity since these changes pe rsist in the presence of the NEP inhibitor, phosphoramidon.