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• W2073275311 abstract "1 In the smooth muscle of the guinea-pig taenia caeci, bradykinin produces a relaxation followed by a contraction. In the presence of hexamethonium and guanethidine, both these phases of the response were insensitive to tetrodotoxin (100 nm), ω-conotoxin GVIA (100 nm) and ibuprofen (1 μm), suggesting that they are due to a direct action on the smooth muscle. 2 The B1 receptor-selective agonist, [des-Arg9]-BK (1–100 μm), was inactive in the taenia caeci, and the B1 receptor-selective antagonist, [Leu8, des-Arg9-BK (1–10 μm), did not inhibit either phase of the bradykinin-induced response. The B2 receptor-selective antagonist, D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]-BK (Hoe 140) (30–300 nm), inhibited both the bradykinin-induced relaxation and contraction with a similar affinity (apparent pKB estimates of 8.5 ± 0.1 and 8.4 ± 0.1 respectively). 3 In a depolarizing high-K+-solution, bradykinin produced concentration-related contractions, though of diminished magnitude; but no relaxation was observed in such media. In Krebs solution, the Ca2+-activated K+-channel blocker, apamin (10 nm), abolished relaxant responses. These observations suggest that contraction results both from membrane potential-dependent, and membrane potential-independent, mechanisms; whereas relaxant responses result entirely from membrane potential-dependent mechanisms. Contractile responses obtained in the high K+-solution were inhibited by D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]-BK with an apparent pKB value of 8.4 ± 0.1. 4 In a Ca2+-free, EGTA-containing medium, relatively high concentrations of bradykinin (> 100 nm) produced transient contractions, suggesting that a component of the contractile response results from release of Ca2+ from an intracellular store. This intracellular Ca2+ store could be refilled in the presence of extracellular Ca2+. The B1 receptor antagonist, [Leu8, des-Arg9-BK (10 μm), did not inhibit this bradykinin-induced contraction, whereas the B2 receptor antagonist, D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]-BK (100 nm) markedly attenuated it (P < 0.001; n = 6). 5 Bradykinin (10 nm-100 μm) significantly elevated tissue levels of total [3H]-inositol phosphates in the presence of Li+, after incubation with myo-[3H]-inositol. The B1 receptor-selective agonist, [des-Arg9-BK (100 μm) did not stimulate [3H]-inositol phosphate formation, and the B1 receptor-selective antagonist, [Leu8, des-Arg9-BK, did not inhibit the formation of [3H]-inositol phosphates in response to a sub-maximal concentration of bradykinin (10 μm; P > 0.05). Two B2 receptor antagonists, D-Arg-[Hyp3, D-Phe7]-BK and D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]-BK, inhibited bradykinin-induced accumulation of total [3H]-inositol phosphates with apparent pKB estimates of 5.4 ± 0.3 and 8.4 ± 0.1, respectively. 6 These data suggest that in the guinea-pig taenia caeci, the five aspects of the action of bradykinin studied (the relaxant and the contractile elements of the biphasic mechanical response, the contractile response in a depolarizing high-K+ solution medium and zero-Ca2+ media, and stimulation of phos-phatidylinositol turnover), all result from activation of B2 receptors. A possible causal relationship is suggested between these B2 receptor-mediated membrane potential-dependent, and -independent events, and their roles in excitation contraction coupling." @default.
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• W2073275311 date "1994-10-01" @default.
• W2073275311 modified "2023-09-29" @default.
• W2073275311 title "Bradykinin B2 receptors and coupling mechanisms in the smooth muscle of the guinea-pig taenia caeci" @default.
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• W2073275311 doi "https://doi.org/10.1111/j.1476-5381.1994.tb17033.x" @default.
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