Contractile responses to histamine and GTP gamma S in beta-escin-treated skinned smooth muscle of guinea pig ileum.
To characterize the calcium (Ca2+)-releasing effects of histamine and GTP gamma S, the drug-induced tension developments were measured in beta-escin-treated skinned longitudinal smooth muscle of guinea pig ileum. Intracellular Ca2+ stores were loaded with Ca2+ by incubating the muscle for 10 min in a Ca(2+)-containing solution. Histamine (10-100 microM), applied after Ca(2+)-loading, produced a transient rise in tension. The effect of histamine was not preserved after treatment with 20 mM caffeine, a Ca(2+)-store releaser. The effect of histamine was potentiated by GTP; inhibited by GDP beta S, 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 GTP gamma S (20 microM) 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 GTP gamma S was completely inhibited by GDP beta S. The initial, transient component of the biphasic GTP gamma S response was abolished or markedly inhibited after treatment with caffeine, heparin or the calcium ionophore A23187. The present results suggest that histamine and GTP gamma S cause a release of Ca2+ from caffeine-sensitive stores which is mediated by IP3 formed through a G-protein-coupled mechanism. The GTP gamma S-induced Ca2+ release is not considered to involve such an IP3-independent process as described in chemically-skinned arterial muscle.
Fukami
K
K
Department of Veterinary Science, Faculty of Agriculture, Gifu University, Japan.
Itagaki
M
M
Komori
S
S
Ohashi
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004928:Escin; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006168:Guinea Pigs; D006493:Heparin / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism
D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004928:Escin; D006632:Histamine; D006160:Guanosine Triphosphate; D006493:Heparin; D002118:Calcium