The rabbit iris sphincter contains NK 1 and NK 3 but not NK 2 receptors: a study with selective agonists and antagonists

Abstract

Tachykinin analogues, claimed to be selective NK 1, NK 2 and NK 3 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 pD 2 values for (Sar 9,Met(O 2) 11)SP (NK 1 receptor agonist), (Nle 10)NKA(4–10) (NK 2 receptor agonist) and (MePhe 7)NKB (NK 3 receptor agonist) were 8.3, 6.1 and 8.2, respectively. (Sar 9,Met(O 2) 11)SP was the most efficacious of the three agonists. The results are compatible with the presence of NK 1 and NK 3 receptors. The low pD 2 value for the NK 2 agonist may reflect a lack of NK 2 receptors and interaction of the NK 2 agonist with NK 1 receptors. The contraction caused by the NK 1 receptor agonist was inhibited competitively by the highly selective NK 1 receptor antagonist (±) CP-96,345; the pA 2 value was 5.5. Also the contraction caused by the NK 2 receptor agonist was inhibited competitively by (±) CP-96,345 with a pA 2 value of 5.7, supporting the view that the two agonists (Sar 9,Met(O 2) 11)SP and (Nle 10NKA(4–10) interact with the same receptor. The selective NK 2 receptor antagonist actinomycin D did not affect the contraction caused by the NK 2 receptor agonist. We conclude that the rabbit iris sphincter muscle contains NK 1 and probably NK 3 receptors. We obtained no evidence for the presence of NK 2 receptors.