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]substance P-(6-11)) and [Sar9]substance P sulfone, both produced concentration-dependent contraction of the circular muscle of the guinea-pig ileum (EC50 values 36 and 84 pM, respectively). The potent and selective NK1 receptor antagonist (+/-)-CP 96,345 antagonized the response to septide with significantly higher affinity than it did the response to [Sar9]substance P sulfone (pA2 values 9.24 and 8.17, respectively) without modifying the response to the selective NK2 receptor agonist, [beta-Ala8]neurokinin A-(4-10). These findings indicate that the septide-sensitive receptor in the circular muscle of the guinea-pig ileum is recognized with high affinity by the NK1 receptor selective antagonist (+/-)-CP 96,345.
Maggi
C A
CA
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Patacchini
R
R
Meini
S
S
Giuliani
S
S
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects*; D015288:Neurokinin A / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D018039:Receptors, Tachykinin; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology
D001713:Biphenyl Compounds; D010446:Peptide Fragments; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D015320:Tachykinins; D013373:Substance P; C054725:septide; D015288:Neurokinin A; C056408:neurokinin A(4-10); D011761:Pyrrolidonecarboxylic Acid; C066892:CP 96345