EVIDENCE FOR THE PRESENCE OF A SEPTIDE-SENSITIVE TACHYKININ RECEPTOR IN THE CIRCULAR MUSCLE OF THE GUINEA-PIG ILEUM

The selective tachykinin NK1 receptor agonists, septide ([Glp6,Pro9]su bstance P-(6-11)) and [Sar9]substance P sulfone, both produced concent ration-dependent contraction of the circular muscle of the guinea-pig ileum (EC50 values 36 and 84 pM, respectively). The potent and selecti ve NK1 receptor antagonist (+/-)-CP 96,345 antagonized the response to septide with significantly higher affinity than it did the response t o [Sar9]substance P sulfone (pA2 values 9.24 and 8.17, respectively) w ithout modifying the response to the selective NK2 receptor agonist, [ beta-Ala8]neurokinin A-(4-10). These findings indicate that the septid e-sensitive receptor in the circular muscle of the guinea-pig ileum is recognized with high affinity by the NK1 receptor selective antagonis t (+/-)-CP 96,345.