BRADYKININ RECEPTORS IN MOUSE AND RAT ISOLATED SUPERIOR CERVICAL-GANGLIA

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 (3 mu 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 (1 mu M). 3 Interleukin 1 beta (30 u ml(-1) for 18 h at 37 degrees C) increased the depolarization caused by bradykinin (3 mu M) in mouse ganglia from 15% to 54% (P < 0.001, n = 12). Responses to the B-1 receptor agonist, [des-Arg(10)]-kallidin (3 mu M) were similarly potentiated but this was only detected after inhibition of peptidase activity with 10 mu M captopril (4% to 35%, n = 5). 4 In ganglia from both species the rank order of agonist potency was bradykinin = [Lys(0)]-bradykinin much less than [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 10 mu 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 1 beta, and by blocking peptide degradation with captopril.