Contractile Responses to Histamine and GTP.GAMMA.S in .BETA.-Escin-Treated Skinned Smooth Muscle of Guinea Pig Ileum.

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To characterize the calcium (Ca2+)-releasing effects of histamine and GTPγS, the drug-induced tension developments were measured in β-escin-treated skinned longitudinal smooth muscle of guinea pig ileum. Intracelluar Ca2+ stores were loaded with Ca2+ by incubating the muscle for 10 min in a Ca2+-containing solution. Histamine (10-100 μM), applied after Ca2+-loading, produced a transient rise in tension. The effect of histamine was not preserved after treatment with 20 mM caffeine, a Ca2+-store releaser. The effect of histamine was potentiated by GTP; inhibited by GDPβS, an antagonist of GTP for binding to G-proteins; or heparin, an antagonist of inositol 1, 4, 5-trisphosphate (IP3) for binding to its receptor; and mimicked by IP3. When GTPγS (20 μM) was applied and continued to be present for 15 min, a transient rise in tension followed by a small, sustained rise in tension was elicited. The effect of GTPγS was completely inhibited by GDPβS. The initial, transient component of the biphasic GTPγS response was abolished or markedly inhibited after treatment with caffeine, heparin or the calcium ionophore A23187. The present results suggest that histamine and GTPγS cause a release of Ca2+ from caffeine-sensitive stores which is mediated by IP3 formed through a G-protein-coupled mechanism. The GTPγS-induced Ca2+ release is not considered to involve such an IP3-independent process as described in chemically-skinned arterial muscle.
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Contractile Responses to Histamine and GTP.GAMMA.S in .BETA.-Escin-Treated Skinned Smooth Muscle of Guinea Pig Ileum.

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