Abstract
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 × 10 −7 M) on preparations desensitized to SP with a concentration of SP of 3 × 10 −7 M. The SP antagonists tested, ( d-Pro 2, d-Phe 7, d-Trp 9)-SP, ( d-Pro 2, d-Trp 7,9)-SP, ( d-Arg 1, d-Pro 2, d-Trp 7,9,Leu 11)-SP and ( d-Arg 1, d-Trp 7,9,Leu 11)-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-Pro 2, d-Phe 7, d-Trp 9)-SP or ( d-Arg 1, d-Pro 2, d-Trp 7,9,Leu 11)-SP. These findings are consistent with the hypothesis that neuronal receptors for SP differ from those on smooth muscle in guinea-pig ileum.
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