This study was designed to investigate the mechanisms by which
bradykinin induces contraction of the pig iris sphincter muscle in vitro. Addition of
bradykinin,
Lys-bradykinin and
Met-Lys-bradykinin to the pig iris sphincter resulted in a graded contraction with a mean EC(50s) of 21, 11 and 5 nM, respectively. The
bradykinin B(1) receptor agonist
des-Arg(9)-bradykinin only caused a slight contraction, measured 6 h after the tissue was set up. The
B(2) receptor antagonists
FR 173657 ((E)-3-(6-acetamido-3-pyridyl)-N [N-2-4-dichloro-3-[(2-methyl-8-quinolinyl) oxymethyl] phenyl]-N-methylamino-carbonyl-ethyl] acrylamide) and
Hoe 140 (D-Arg(0)-[Hyp(3), Thi(5), D-
Tic(7), Oic(8)]-
bradykinin produced a graded shift to the right associated with marked inhibition of the
bradykinin-induced contraction.
Atropine,
guanethidine or
tetrodotoxin significantly reduced the
bradykinin-induced contraction.
Dazoxiben, an inhibitor of
thromboxane A(2), and
MK-571 (3-(3-(2-(7-chloro-2-quinolinyl) ethenyl) phenyl ((3-dimethyl amino-3oxo-propyl) thio) methyl)
propanoic acid, a
leukotriene D(4) receptor-selective antagonist, also caused inhibition of the
bradykinin-mediated contraction.
Cyclooxygenase-1 and -2 inhibitors,
indomethacin,
ibuprofen, valeryl
salicylate and
NS 398 (N-[2-(cyclohexyloxy)-4-nitrophenyl]methanosulfonamide) all significantly inhibited the
bradykinin-mediated contraction without affecting the
carbachol-induced contraction of the pig iris sphincter. Taken together, these results indicate that the
bradykinin-mediated contraction of the pig iris sphincter muscle seems to be mediated primarily by the activation of the
B(2) receptor release of
acetylcholine,
noradrenaline and both
cyclooxygenase-1 and -2 metabolites besides the release of
leukotriene D(4) and tromboxane A(2) from the
arachidonic acid pathway.