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THE MECHANISM OF ACTION OF A SUBSTANCE P ANTAGONIST (D‐Pro2, D‐Trp7,9)‐SP

1 A newly synthesized substance P (SP) analogue, (d‐Pro2, d‐Trp7,9)‐SP, specifically antagonizes the contractile effects of SP on the guinea‐pig isolated taenia coli. In addition, previous studies had indicated that the SP analogue per se is capable of contracting this preparation. The results of the present study on the guinea‐pig taenia suggest that the smooth muscle contractions produced by the SP analogue are due to histamine release. No contractions were observed following blockade of histamine H1‐receptors by mepyramine or following pretreatment with the histamine liberating agent, compound 48/80. 2 Analysis of the inhibition of SP‐induced contraction by the analogue suggests that the inhibition is of the competitive type; pA2 was calculated to be 6.1. 3 We conclude that (d‐Pro2, d‐Trp7,9)‐SP is a competitive SP antagonist with histamine‐releasing properties.