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Receptors mediating tachykinin‐induced contractile responses in guinea‐pig trachea
Author(s) -
Ireland S.J.,
Bailey F.,
Cook A.,
Hagan R.M.,
Jordan C.C.,
StephensSmith M.L.
Publication year - 1991
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.1476-5381.1991.tb09812.x
Subject(s) - tachykinin receptor , receptor , guinea pig , substance p , antagonist , medicine , endocrinology , neurokinin a , biology , chemistry , neuropeptide
1 The classification of tachykinin receptors in the guinea‐pig trachea has been investigated. This was of interest because, from previous studies, it was not clear whether the guinea‐pig trachea contains either a mixture of NK 1 and NK 2 receptors or, alternatively, a single type of novel tachykinin receptor. 2 In the present study, the guinea‐pig trachea was contracted by tachykinin agonists selective for NK 1 receptors (substance P methylester (SPOMe) and GR73632) or NK 2 receptors (GR64349) but not NK 3 receptors (senktide). 3 Against SPOMe and GR73632, the NK 1 antagonist, GR71251, behaved as a reversible competitive antagonist having apparent affinity (pK B 7.05 vs SPOMe) consistent with action at NK 1 receptors. GR71251 (3 μ m ) did not antagonize responses to GR64349. 4 The NK 2 antagonists L‐659,877 and Ac‐Leu‐Asp‐Gln‐Trp‐Phe‐Gly‐NH 2 (R396) antagonized GR64349 although only R396 appeared to behave competitively (pK B 5.73). Neither L‐659,877 (30 μ m ) nor R396 (30 μ m ) blocked responses to SPOMe. 5 For L‐659,877 and R396, comparison was made between activity in guinea‐pig trachea and in preparations known to contain tachykinin receptors predominantly of the NK 2 type. In the rabbit trachea, both L‐659,877 and R396 had effects similar to those in guinea‐pig trachea. In contrast, in the rat colon muscularis mucosae, both L‐659,877 and R396 appeared to behave competitively with pK B values against GR64349 of 7.83 and 6.90 respectively. 6 It is concluded that in guinea‐pig trachea, contractile responses can be induced by activation of both NK 1 and NK 2 receptors. The present data are discussed with reference to the proposed existence of subtypes of the NK 2 receptor.