Substance P antagonists and mucociliary activity in rabbit.

Substance P (SP) is known to accelerate mucociliary (m.c.) activity in the rabbit maxillary sinus in vivo. The physiological significance of this finding was investigated by testing three putative SP antagonists. [Arg5, D-Trp7,9, Nle11]SP5-11 could not be used as an antagonist because it stimulated m.c. activity. [D-Arg1, D-Trp7,9, Leu11]SP had no effect on the m.c. activity changes induced by SP. [D-Pro2, D-Trp7,9]SP was found to be an effective antagonist, 1 mg/kg of this drug reversibly inhibiting both the effects of 0.1 micrograms/kg SP and the stimulating effect of 1.0 micrograms/kg bradykinin and 30.0 micrograms/kg capsaicin; the stimulating effect of 0.5 micrograms/kg methacholine was not inhibited. It is suggested that bradykinin and capsaicin stimulate m.c. activity at least partly by releasing SP. The results of this investigation also support the view that the accelerating effect of SP on m.c. activity reflects physiological SP-mediated protective mechanisms in the airways. It is concluded that [D-Pro2,D-Trp7,9]SP is a useful pharmacological tool for studying the role of SP in the control of m.c. activity in rabbits.