Premium
Bradykinin receptors in mouse and rat isolated superior cervical ganglia
Author(s) -
Seabrook G.R.,
Bowery B.J.,
Hill R.G.
Publication year - 1995
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.1476-5381.1995.tb15887.x
Subject(s) - bradykinin , kallidin , medicine , endocrinology , agonist , bradykinin receptor , depolarization , chemistry , receptor , kinin , receptor antagonist , biology , antagonist , pharmacology
1 The ability of bradykinin and its analogues to depolarize rat and mouse superior cervical ganglia was studied by use of in vitro grease‐gap recording techniques, and the ability of antagonists selective for bradykinin receptor subtypes to block their effects was examined. 2 Bradykinin (μ m ) depolarized ganglia from both species, although the magnitude of the maximal response was less in mouse (15 ± 5%, n = 7) than rat tissue (33 ± 6%, n = 7), relative to muscarine (1μ m ). 3 Interleukin 1β (30 u ml −1 for 18 h at 37°C) increased the depolarization caused by bradykinin (3μ m ) in mouse ganglia from 15% to 54% (P<0.001, n =12). Responses to the B 1 receptor agonist, [des‐Arg 10 ]‐kallidin (3μ m ) were similarly potentiated but this was only detected after inhibition of peptidase activity with 10FM captopril (4% to 35%, n = 5). 4 In ganglia from both species the rank order of agonist potency was bradykinin = [Lys 0 ]‐bradykinin >> [des‐Arg 10 ]‐kallidin. However, like responses to [des‐Arg 10 ]‐kallidin in mouse tissue, both the potency of bradykinin and the maximal depolarization achieved (EC 50 = 912 nM; 80%, n = 11) was enhanced following inhibition of angiotensin converting enzyme with 10μ m captopril (EC 50 = 50 nM; 135%, n = 4). 5 Responses to bradykinin were selectively antagonized by the B 2 receptor antagonist, Hoe 140 but not by the B 1 antagonist, [Leu 8 ]‐bradykinin 1–8 . From Schild analysis the pA 2 value for Hoe 140 in mouse tissue was 9.65, although the slope of the regression line was significantly greater than unity, indicating non‐competitive kinetics (slope = 1.88 ± 0.18, n = 9). The depolarization caused by [Lys 0 ]‐bradykinin was also antagonized by Hoe 140 (3 nM). 6 Thus the predominant bradykinin receptor in mouse superior cervical ganglia is compatible with a B 2 subtype. Furthermore the depolarizations caused by B 1 and B 2 agonists in this tissue can be increased following exposure to interleukin 1β, and by blocking peptide degradation with captopril.