Inositol 1,4,5-trisphosphate activates pharmacomechanical coupling in smooth muscle of the rabbit mesenteric artery.

摘要: To clarify the nature of noradrenaline (NA)-induced contraction, effects NA on inositol phospholipid metabolism and actions 1,4,5-trisphosphate (InsP3) skinned muscle rabbit mesenteric artery were investigated. NA, in concentrations over 1 nM, reduced amount phosphatidylinositol 4,5-bisphosphate (PI-P2) increased phosphatidic acid (PA). The maximum reduction PI-P2 increase PA observed presence microM-NA. With prolonged application was gradually restored to near control level, but with repeated applications separated by rinses Krebs solution, there a consistent PI-P2. NA-induced breakdown inhibited alpha 1-adrenoceptor blocking agent, prazosin. After incubation tissue radioactive inositol-containing transiently InsP3 which followed increases 1,4-bisphosphate (InsP2) monophosphate (InsP). accumulation Ca saponin-treated cells dog dispersed collagenase, released stored InsP2 did not. A23187 (5 microM) not (up 10 microM), depleted accumulated ATP. In tissues, 0.3 microM, produced contraction following into store site. from same source as caffeine. release appeared concentration-dependent manner this also depended (the median effective dose (ED50) 3.0 microM 0.1 microM-Ca 1.0 microM-Ca). We concluded that activates 1-adrenoceptors, thus hydrolysing synthesizing InsP3. This product can estimated reduces residual cells. Contraction evoked through pharmacomechanical coupling be explained function