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Characterization of the tachykinin NK 2 receptor in the human bronchus: influence of amastatin‐sensitive metabolic pathways
Author(s) -
Astolfi Mara,
Treggiari Stefano,
Giachetti Antonio,
Meini Stefania,
Maggi Carlo Alberto,
Manzini Stefano
Publication year - 1994
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.1476-5381.1994.tb14775.x
Subject(s) - neurokinin a , aminopeptidase , agonist , receptor , medicine , endocrinology , partial agonist , biology , biochemistry , leucine , amino acid , substance p , neuropeptide
1 The aim of this study was to characterize the tachykinin NK 2 receptor subtype mediating the spasmogenic response in the human isolated bronchus. The motor response to neurokinin A (NKA) and the selective NK 2 agonist [βAla 8 ]NKA(4–10), as well as the antagonistic effects of cyclic (L659,877) and linear (MEN 10376) peptide NK 2 antagonists were assessed in the presence or absence of amastatin (an inhibitor of aminopeptidases A and M). 2 NKA was more potent than [βAla 8 ]NKA(4–10) in eliciting bronchoconstriction (pD 2 being 7,43 and 6,87 respectively). In the presence of amastatin (1 μ m ), the estimated affinity of [βAla 8 ]NKA(4–10), but not that of NKA, was significantly increased to yield a pD 2 of 7,44. 3 L659,877 and MEN 10376 inhibited [βAla 8 ]NKA(4–10)‐induced contraction with similar affinities; pA 2 values were 5.7 ± 0.22 and 6.3 ± 0.32, respectively. Amastatin (1 μ m ) increased the potency of MEN 10376 to 7.28 ± 0.46, whereas that of L659,877 was unaffected. 4 In the presence of amastatin the pseudopeptide MDL 28,564 behaved as a partial agonist. 5 We conclude that the NK 2 receptor subtype present in the human bronchus has properties similar to those described for the circular muscle of the human colon and thus may be classified as a ‘NK 2A ’ subtype. We show that the apparent potency of peptides, bearing N‐terminal acidic residues, is influenced by an amastatin‐sensitive peptidase, possibly aminopeptidase A.