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Tachykinin receptors mediating responses to sensory nerve stimulation and exogenous tachykinins and analogues in the rabbit isolated iris sphincter
Author(s) -
Hall Judith M.,
Mitchell Debra,
Morton Ian K.M.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13721.x
Subject(s) - neurokinin a , substance p , agonist , tachykinin receptor , receptor , stimulation , endocrinology , medicine , chemistry , bradykinin , tachykinin receptor 1 , contraction (grammar) , neurokinin b , receptor antagonist , neuropeptide , antagonist , biology
1 We have used selective tachykinin receptor agonists and antagonists to investigate the nature of the receptors mediating responses to endogenous and exogenous tachykinins in the rabbit iris sphincter preparation in vitro . 2 The NK 1 ‐selective agonist, substance P methyl ester, induced contraction with a pD 2 of 9.16 indicating the presence of NK 1 receptors. In confirmation, the NK 1 ‐selective antagonist, GR82334, competitively antagonized responses to substance P methyl ester with high affinity (p K B 7.46). 3 NK 3 receptors also mediate contraction since NK 3 ‐selective agonists exhibited high potency, e.g. the pD 2 of [Me‐Phe 7 ]‐neurokinin B was 9.67, and their responses were not inhibited by GR82334 (10 μ m ). 4 NK 2 receptor activation does not seem to contribute to contraction since the NK 2 ‐selective agonist [β‐Ala 8 ]‐neurokinin A(4–10) had relatively low potency (pD 2 6.43), and the NK 2 ‐selective antagonists MEN10207 (1 μ m ) and L‐659,877 (10 μ m ) were inactive or had low affinity, respectively. 5 GR82334 (1 μ m ) significantly inhibited responses to electrical field‐stimulation of non‐adrenergic non‐cholinergic sensory nerves (3, 10 and 30 Hz), and caused a rightward shift of the log concentration‐response curve to bradykinin (lateral shift ca . 1000 fold). Higher concentrations of GR82334 (10 μ m ) significantly attenuated responses to capsaicin (1–60 μ m ) whilst completely abolishing responses to field‐stimulation (3, 10 and 30 Hz) and bradykinin (1 n m – 3 μ m ). 6 In conclusion, NK 1 and NK 3 receptor activation results in contraction of the rabbit iris sphincter. The contractile response following sensory nerve stimulation by bradykinin, capsaicin and electrical field stimulation results from NK 1 receptor activation.