Altered reactivity of gastric fundus smooth muscle in the mouse with targeted disruption of the kinin B1 receptor gene.
Relaxing action of sodium nitroprusside (SNP) was significantly reduced in the stomach fundus of mice lacking the kinin B(1) receptor (B(1)(-/-)). Increased basal cGMP accumulation was correlated with attenuated SNP induced dose-dependent relaxation in B(1)(-/-) when compared with wild type (WT) control mice. These responses to SNP were completely blocked by the guanylate cyclase inhibitor ODQ (10 microM). It was also found that Ca(2+)-dependent, constitutive nitric oxide synthase (cNOS) activity was unchanged but the Ca(2+)-independent inducible NOS (iNOS) activity was greater in B(1)(-/-) mice than in WT animals. Zaprinast (100 microM), a specific phosphodiesterase inhibitor, increased the nitrergic relaxations and the accumulation of the basal as well as the SNP-stimulated cGMP in WT but not in B(1)(-/-) stomach fundus. From these findings it is concluded that the inhibited phosphodiesterase activity and high level of cGMP reduced the resting muscle tone, impairing the relaxant responses of the stomach in B(1)(-/-) mice. In addition, it can be suggested that functional B(2) receptor might be involved in the NO compensatory mechanism associated with the deficiency of kinin B(1) receptor in the gastric tissue of the transgenic mice.
Department of Biophysics, Universidade Federal de São Paulo-Escola Paulista de São Paulo, São Paulo, Brazil.
Ana M R B
AM
Barbosa
Sandra A
SA
Felipe
Ronaldo C
RC
Araujo
Elisa M
EM
Kawamoto
Maria H C
MH
Carvalho
Cristoforo
C
Scavone
João B
JB
Pesquero
Suma I
SI
Shimuta
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D043783:Receptor, Bradykinin B1 / Q000235:genetics*; D013270:Stomach / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*
D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D043783:Receptor, Bradykinin B1; D009599:Nitroprusside; D019001:Nitric Oxide Synthase; C011145:zaprinast; D006152:Cyclic GMP