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Further evidence for the existence of NK 2 tachykinin receptor subtypes
Author(s) -
Patacchini Riccardo,
Astolfi Mara,
Quartara Laura,
Rovero Paolo,
Giachetti Antonio,
Maggi Carlo Alberto
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.tb12390.x
Subject(s) - tachykinin receptor , receptor , biology , endocrinology , medicine , neuroscience , chemistry , substance p , neuropeptide
1 We have evaluated the biological activity of a number of neurokinin A (4–10), (NKA (4–10)) analogues in the endothelium‐deprived rabbit isolated pulmonary artery (RPA) and hamster isolated trachea (HT), two tissues rich in different NK 2 receptor subtypes. 2 MDL 28,564, a pseudopeptide selective for NK 2 receptor sites, behaved as a full agonist in the RPA, while in the HT it competitively antagonized NKA or [βAla 8 ]‐NKA (4–10) contractile effects. 3 The peculiar behaviour of MDL 28,564 in the RPA and HT may be explained neither by a difference in receptor reserve between the two organs (the reserve being three times greater in RPA than in the HT) nor by a different affinity for the two receptor subtypes (identical dissociation constants, p K A or p K B , calculated in the RPA and in the HT). On the other hand, MDL 28,564 displayed a very different intrinsic efficacy for the two receptor subtypes. 4 The novel peptides MEN 10,295 ([Trp 7 , βAla 8 ]‐NKA‐(4–10)) and MEN 10,296 ([Tyr 5 , Trp 7 , βAla 8 ]‐NKA‐(4–10)) behaved as weaker agonists than MDL 28,564 in the RPA, but retained appreciable agonist activity also in the HT. 5 The novel peptides: MEN 10,282 ([Tyr 5 , d ‐Trp 6,8 , Trp 9 , Arg 10 ]‐NKA‐(4–10)), MEN 10,449 ([diI‐Try 5 , d ‐Trp 6,8,9 , Arg 10 ]‐NKA‐(4–10)) and the cyclic hexapeptide L 659,877 (cyclo [Leu‐Met‐Gln‐Trp‐Phe‐Gly]) behaved as competitive antagonists against NKA contractile effects both in the RPA and HT. MEN 10,282 and MEN 10,449 were unable to distinguish between the NK 2 receptor subtypes, having almost the same affinity in the two organs. On the other hand L 659,877 was about 15 times more potent in the HT than in the RPA. 6 These results provide further evidence for NK 2 receptors heterogeneity and are useful in outlining pharmacological features of the two subtypes present in the RPA and HT.