The rabbit iris sphincter contains NK1 and NK3 but not NK2 receptors: a study with selective agonists and antagonists

Tachykinin analogues, claimed to be selective NK1, NK2 and NK3 receptor agonists, contracted the isolated rabbit iris sphincter muscle in a concentration-dependent manner. The contractions were not modified by the enkephalinase inhibitor thiorphan and the angiotensin-converting enzyme inhibitor captopril (10(-5) M of each). The pD2 values for (Sar9,Met(O2)11)SP (NK1 receptor agonist), (Nle10)NKA(4-10) (NK2 receptor agonist) and (MePhe7)NKB (NK3 receptor agonist) were 8.3, 6.1 and 8.2, respectively. (Sar9,Met(O2)11)SP was the most efficacious of the three agonists. The results are compatible with the presence of NK1 and NK3 receptors. The low pD2 value for the NK2 agonist may reflect a lack of NK2 receptors and interaction of the NK2 agonist with NK1 receptors. The contraction caused by the NK1 receptor agonist was inhibited competitively by the highly selective NK1 receptor antagonist (+/-) CP-96,345; the pA2 value was 5.5. Also the contraction caused by the NK2 receptor agonist was inhibited competitively by (+/-) CP-96,345 with a pA2 value of 5.7, supporting the view that the two agonists (Sar9,Met(O2)11)SP and (Nle10)NKA(4-10) interact with the same receptor. The selective NK2 receptor antagonist actinomycin D did not affect the contraction caused by the NK2 receptor agonist. We conclude that the rabbit iris sphincter muscle contains NK1 and probably NK3 receptors. We obtained no evidence for the presence of NK2 receptors.