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Bradykinin B2 receptors and coupling mechanisms in the smooth muscle of the guinea-pig taenia caeci
| Content Provider | Scilit |
|---|---|
| Author | Field, Julie L. Butt, Semal K. Morton, Ian K. M. Hall, Judith M. |
| Copyright Year | 1994 |
| Description | Journal: British Journal of Pharmacology |
| 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 $B_{1}$ receptor-selective agonist, $[des-Arg_{9}$]-BK (1–100 μm), was inactive in the taenia caeci, and the $B_{1}$ receptor-selective antagonist, [Leu8, $des-Arg_{9}$-BK (1–10 μm), did not inhibit either phase of the bradykinin-induced response. The $B_{2}$ receptor-selective antagonist, $D-Arg-[Hyp^{3}$, $Thi^{5}$, $D-Tic^{7}$, $Oic^{8}$]-BK (Hoe 140) (30–300 nm), inhibited both the bradykinin-induced relaxation and contraction with a similar affinity (apparent $pK_{B}$ 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 $Ca^{2+}$-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 $D-Arg-[Hyp^{3}$, $Thi^{5}$, $D-Tic^{7}$, $Oic^{8}$]-BK with an apparent $pK_{B}$ value of 8.4 ± 0.1. 4 In a $Ca^{2+}$-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 $Ca^{2+}$ from an intracellular store. This intracellular $Ca^{2+}$ store could be refilled in the presence of extracellular $Ca^{2+}$. The $B_{1}$ receptor antagonist, $[Leu^{8}$, $des-Arg^{9}$-BK (10 μm), did not inhibit this bradykinin-induced contraction, whereas the $B_{2}$ receptor antagonist, $D-Arg-[Hyp^{3}$, $Thi^{5}$, $D-Tic^{7}$, $Oic^{8}$]-BK (100 nm) markedly attenuated it (P < 0.001; n = 6). 5 Bradykinin (10 nm-100 μm) significantly elevated tissue levels of total $[^{3}$H]-inositol phosphates in the presence of $Li^{+}$, after incubation with $myo-[^{3}$H]-inositol. The $B_{1}$ receptor-selective agonist, $[des-Arg^{9}$-BK (100 μm) did not stimulate $[^{3}$H]-inositol phosphate formation, and the $B_{1}$ receptor-selective antagonist, $[Leu^{8}$, $des-Arg^{9}$-BK, did not inhibit the formation of $[^{3}$H]-inositol phosphates in response to a sub-maximal concentration of bradykinin (10 μm; P > 0.05). Two $B_{2}$ receptor antagonists, $D-Arg-[Hyp^{3}$, $D-Phe^{7}$]-BK and $D-Arg-[Hyp^{3}$, $Thi^{5}$, $D-Tic^{7}$, $Oic^{8}$]-BK, inhibited bradykinin-induced accumulation of total $[^{3}$H]-inositol phosphates with apparent $pK_{B}$ 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 $zero-Ca^{2+}$ media, and stimulation of phos-phatidylinositol turnover), all result from activation of $B_{2}$ receptors. A possible causal relationship is suggested between these $B_{2}$ receptor-mediated membrane potential-dependent, and -independent events, and their roles in excitation contraction coupling. |
| Related Links | http://europepmc.org/articles/pmc1510129?pdf=render https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.1994.tb17033.x |
| Ending Page | 613 |
| Page Count | 7 |
| Starting Page | 607 |
| e-ISSN | 14765381 |
| DOI | 10.1111/j.1476-5381.1994.tb17033.x |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 113 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 1994-10-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: British Journal of Pharmacology Bradykinin Receptors Bradykinin B2 Receptors Bradykinin Receptor Antagonists Bradykinin Receptor Mechanisms Taenia Caeci (guinea-pig) Electromechanical Coupling Pharmacomechanical Coupling Phosphatidylinositol Turnover Ca2+-activated K+-channel |
| Content Type | Text |
| Resource Type | Article |
