Effect of substance P on neurally mediated contraction of rabbit airway smooth muscle

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Abstract
The neuromodulatory action of substance P (SP) was investigated in isolated rabbit tracheal smooth muscle (TSM) segments contracted with electrical field stimulation (ES). The tissues were placed in organ baths containing modified Kreb-Ringer solution and stimulated at a constant voltage (8 V; 24.5 mA) and pulse duration (2 ms) with ES frequencies ranging from 1 to 100 Hz. In the presence of SP, there occurred a dose-dependent augmentation of the TSM contractile response to any given ES, with the maximal effect of SP obtained at a dose of 10-7 M. Accordingly, with the administration of 10-7 M SP, the ES frequency-response relationship was altered so that 1) the mean (.+-. SE) maximal tension (Tmax) induced by ES significantly increased (P < 0.02) from a base-line value of 273 .+-. 53 to 402 .+-. 45 g/g TSM; and 2) the mean (.+-. SE) log ES frequency producing 50% of Tmax (ES50) significantly decreased from a base-line value of 1.278 .+-. 0.069 to 1.102 .+-. 0.070 Hz (P < 0.01). In contrast to these effects on ES-induced contraction, SP administration did not affect the TSM contractile response to administered methacholine chloride (10-8 to 10-3 M). On the other hand, the effects of SP on ES-induced contraction were independently blocked by the cholinergic antagonist, atropine (10-6 M), the neurotoxin, tetrodotoxin (10-6 g/ml); and the SP antagonist, D-Arg1,D-Pro2,D-Trp7,9,Leu11-SP (10-5 M). Thus, since SP 1) augments the neurally mediated (tetrodotoxin-sensitive) TSM contractile response to ES but 2) has no effect on TSM sensitivity to an administered cholinergic agonist, these findings suggest that SP accelerates the prejunctional endogenous neural release of acetylcholine while having no effect on cholinergic receptor binding at the airway neuromuscular junction.