Bombesin-induced contractions of guinea pig lung strips are modulated by endogenous nitric oxide.
We have investigated the effects of a nitric oxide (NO) biosynthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on the bombesin-evoked contraction of guinea pig parenchymal lung strips. The bombesin-induced contractions of lung strips were significantly increased after L-NAME (300 micro)) pre-treatment. The maximal response was increased (P < 0.01) by 37% after L-NAME treatment when compared with the control group. The pD2 value was not influenced by L-NAME pre-treatment. The enhancement of the bombesin-induced contraction caused by L-NAME was reversed by addition of an excess of the NO precursor L-arginine (600 microM) but not by the addition of its inactive enantiomer D-arginine (600 microM). Like L-NAME, methylene blue (1 microM), an agent that inhibits the soluble guanylyl cyclase activated by NO, significantly increased (P < 0.01) the maximal contraction induced by bombesin (183 +/- 16 mg) when compared with the control group (141 +/- 15 mg). When tested against other agonist-induced contractions, L-NAME did not change the responsiveness of parenchymal lung strips to bradykinin or carbachol but significantly increased lung contraction induced by histamine. NO synthesis inhibition resulted in a pronounced increase in the bombesin-induced contraction of guinea-pig lung strips. Our results suggest that bombesin contributes to NO synthesis and release which then acts to reduce the contraction of the lungstrip in response to bombesin.
Lach
E
E
Laboratoire de Neuroimmunopharmacologie pulmonaire, INSERM U 425, Université Louis Pasteur-Strasbourg I, Illkirch, France.
Daeffler
L
L
Waeldelé
F
F
Gies
J P
JP
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001839:Bombesin / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*
D009569:Nitric Oxide; D001120:Arginine; D001839:Bombesin; D019331:NG-Nitroarginine Methyl Ester