Disruption of the kinin B1 receptor gene affects potentiating effect of captopril on BK-induced contraction in mice stomach fundus.
A transgenic mouse model, deficient in kinin B(1) receptor (B(1)(-/-)) was used to evaluate the role of B(2) receptor in the smooth muscle stomach fundus. The results showed that the potency of bradykinin (BK) to induce contraction in the gastric tissue was maintained whereas the efficacy was markedly reduced. The angiotensin converting enzyme (ACE) inhibitor captopril potentiated BK-induced effect in wild type (WT) but not in B(1)(-/-) fundus. However, ACE activity detected by the convertion of Ang I to Ang II was inhibited by captopril in both types of gastric tissues. Taking into account the hypothesis that captopril and ACE bind to the B(2) receptor, we suggest that this complex was not formed in the stomach deficient in B(1) receptor. Therefore, our finding strongly support the hypothesis that in smooth muscles that constitutively express the kinin B(1) and B(2) receptors, an interaction between captopril and ACE, B(1) and B(2) receptors should occur forming a complex protein interaction for the potentiating effect of ACE on kinin receptors.
Barbosa
Ana M R B
AM
Departament of Biophysics, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Botucatu 862, 04023-062 São Paulo, S.P., Brazil.
Felipe
Sandra A
SA
Pesquero
João B
JB
Paiva
Antonio C M
AC
Shimuta
Suma I
SI
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D004357:Drug Synergism; D005753:Gastric Mucosa / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D043783:Receptor, Bradykinin B1 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D043783:Receptor, Bradykinin B1; D002216:Captopril