Effects of substance P antagonists on the atropine-sensitive and atropine-resistant responses of guinea-pig ileum to substance P.

The effects of substance P (SP) antagonists on the atropine-sensitive and atropine-resistant responses to SP of guinea-pig isolated ileum were investigated. The atropine-resistant response to SP was the contractile response on untreated preparations, and the atropine-sensitive response was the response to high concentrations of SP (5 X 10(-7) M) on preparations desensitized to SP with a concentration of SP of 3 X 10(-7) M. The SP antagonists tested, (D-Pro2,D-Phe7,D-Trp9)-SP, (D-Pro2,D-Trp7,9)-SP, (D-Arg1,D-Pro2,D-Trp7,9,Leu11)-SP and (D-Arg1,D-Trp7,9,Leu11)-SP (spantide), did not have similar orders of potency on the atropine-sensitive and atropine-resistant responses to SP, spantide being more potent than the other antagonists on the atropine-resistant response but no more potent on the atropine-sensitive response than (D-Pro2,D-Phe7,D-Trp9)-SP or (D-Arg1,D-Pro2,D-Trp7,9,Leu11)-SP. These findings are consistent with the hypothesis that neuronal receptors for SP differ from those on smooth muscle in guinea-pig ileum.