Bradykinin-induced contraction of guinea pig lung in vitro.
We have investigated the contractile effect of bradykinin (BK) in guinea pig lung in vitro. BK induces a dose-related contraction of lung parenchymal strips which is increased significantly in the presence of 10(-5) M captopril (an angiotensin converting enzyme inhibitor) or 10(-5) M DL-thiorphan (a neutral endopeptidase inhibitor). The kininase I inhibitor, DL-2-mercaptomethyl-3-guanidino-ethylthiopropionic acid (MGTPA), has no effect on the BK-induced contraction. BK is more potent in contracting parenchymal lung strips than other contractile agents (histamine, carbachol and substance P), however the BK-induced maximal contraction is lower than those obtained with histamine and carbachol. The B1 agonist, des-Arg9-BK, does not contract lung parenchymal strips. The new BK B2 receptor antagonists (Hoe 140, NPC 17731 and NPC 17761), which possess binding affinities in the nanomolar range, inhibit the BK-induced contractile response in a dose-dependent manner. The BK-induced contraction was unaffected by propranolol, atropine, tetrodotoxin, capsaicin pre-treatment, triprolidine, methysergide, Ro 19-3704 and N omega-nitro-L-arginine-methyl-ester (L-NAME), excluding the involvement of nervous pathways, preformed mast cell mediators, platelet-activating factor and nitric oxide. However, indomethacin, a cyclooxygenase inhibitor, AA-861, a 5-lipoxygenase inhibitor, and furegrelate, a thromboxane A2 synthase inhibitor, decreased the contractile response to BK, suggesting that both cyclooxygenase and 5-lipoxygenase products are involved in this contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Lach
E
E
Laboratoire de Neuroimmunopharmacologie Pulmonaire, INSERM CJF-9105, Université Louis Pasteur Strasbourg I, Illkirch, France.
Trifilieff
A
A
Mousli
M
M
Landry
Y
Y
Gies
J P
JP
D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D004789:Enzyme Activation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D011480:Protease Inhibitors / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
D007295:Inositol Phosphates; D011480:Protease Inhibitors; D010738:Type C Phospholipases; D001920:Bradykinin