| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
|
|---|
| Research Abstract |
In pregnant uterine smooth muscle cells, calcium (Ca^<2+>) plays an essential role in triggering contraction, as obserbed in other visceral smooth muscles. An increase of intracellular Ca^<2+> ([Ca^<2+>]i") in myometrial cells forms Ca^<2+>-calmodulin complex and phosphorylate myosin light chain and thus initiates myometrial cell contractions. To study the mechanism of contraction regulated by Ca^<2+>, chemically skinned muscle technique which permits membrane permeabilization and "chemical clamping of [Ca^<2+>]i" has been developed in smooth muscles of rat or human myometrium. Recently, it has been reported that agonist coupling to receptors increases Ca^<2+> sencitivity for contractile protein of vascular smooth muscles through activation of unidentified G-proteins. In pregnant rat myometrium, the maximum amplitude of tension induced by carbachol was much greater than that by KC1 in intact strips using calcium indicator while the maximum increase of [Ca^<2+>]i were alsmost same. In b
… More
eta-escin treated skinned myometrial strips from late gestation, 0.3 muM Ca^<2+> evoked contractions. Carbachol plus GTP or oxytocin plus GTP enhanced the 0.3 muM Ca^<2+>-induced contractions of skinned strips and the increase was antagonized by GDPbetaS.GTPgammaS,PGF2alpha plus GTP,PGE2 plus GTP,okadaic acid and protein kinase C (PKC) stimulated by PDBu also augmented 0.3 muM Ca^<2+> contractions in skinned strips. These results suggest that agonists, such as corbachol, oxytocin, PGs enhanced the Ca^<2+>-induced contraction of myometrium through G-protein mediated mechanism. These agonists/G-protein mediated Ca^<2+>-sensitizing effects on contractile elements might produces the additional contractile force with same amount of [Ca^<2+>]i this providing expelling forces for delivering of fetuses. In addition, nitric oxide, which stiimulates guanylate cyclase in the muscle cells to produce cGMP,inhibit pharmaco-mechanical coupling, contractile apparatus and Ca^<2+> extrusion system in pregnant rat myometrium. We believe that clarification of these intracellular phenomenon is usefull for the prevention of premature labor. Less
|
