Direct effect of opioid receptor stimulation on CaィイD12+ィエD1 transients and contraction in intact guinea pig beating heat

(1)We investigated the effect of morphine on intracellular Ca I D12+I D 1 concentration([Ca I D 12+I D 1]i)and left ventricular pressure(LVP)relationship in intact beating hearts isolated from guinea pigs，and using specificκ-，δI D 21 ii D 2-，andδI D 22 d 2-，opioid antagonists，which opioid stimulation is related to the direct cardiac effect of morphine.Morphine(1µM)decreases available without decreasing[Ca I D 12+I D 1]i cardiac contraction，and it enhances myofilament Ca I D 12+I D 1 sensitivity in intact beating hearts.The decrease of Ca I D12+D 1 transients induced by morphine would be mainly cause byδI D 21个D 2-，andδI D 22个D 2-opioid stimulation，but notκopioid stimulation.(2)δI D 21个D 2-opioid agonist(TAN-67，1µM)decreased both LVP and[Ca I D 12+I D 1]i，but not LVP.The cardiac effects induced byδ-D21--D2-，andδD22-D2-antagonist，respectively.Theδ-D21-D2-，andδ-D22-D2-agonists caused a leftward shift in the curve of developed LVP as a function of available[Ca D12+D1]i，and it was indicated that these agonists enhanced myofilament Ca D12+D1sensitivity.(3)Propofol decreases available[Ca D12+I D1]i without decreasing cardiac contraction，and it enhances myilament Ca c12+decreasing cardiac contraction，and it enhances myilament Caases available[Ca D12+I D1]i without decreasing cardiac contraction，and it enhances myilament Caases available[Ca D12+I D1]。The inhibition of available[Ca I D 12+I D 1]i by propofol may be mainly mediated by an impairment of sarcoplasmic reticulum Ca I D 12+I D 1 handling rather than the sarcolemmal L-type Ca I D 12+I D 1 current.

(1) We investigated the effect of morphine on intracellular CaィイD12+ィエD1 concentration ([CaィイD12+ィエD1]i) and left ventricular pressure (LVP) relationship in intact beating hearts isolated from guinea pigs, and using specific κ-,δィイD21ィエD2-, and δィイD22ィエD2-, opioid antagonists, which opioid stimulation is related to the direct cardiac effect of morphine . Morphine (1μM) decreases available without decreasing [CaィイD12+ィエD1]i cardiac contraction, and it enhances myofilament CaィイD12+ィエD1 sensitivity in intact beating hearts. The decrease of CaィイD12+ィエD1 transients induced by morphine would be mainly cause by δィイD21ィエD2-, and δィイD22ィエD2-opioid stimulation, but not κ opioid stimulation.(2) δィイD21ィエD2-opioid agonist (TAN-67, 1μM) decreased both LVP and [CaィイD12+ィエD1]i, but not LVP. The cardiac effects induced by δィイD21ィエD2-, and δィイD22ィエD2-antagonist, respectively. The δィイD21ィエD2-, and δィイD22ィエD2-agonists caused a leftward shift in the curve of developed LVP as a function of available [CaィイD12+ィエD1]i, and it was indicated that these agonists enhanced myofilament CaィイD12+ィエD1 sensitivity.(3) Propofol decreases available [CaィイD12+ィエD1]i without decreasing cardiac contraction, and it enhances myofilament CaィイD12+ィエD1 sensitivity in intact beating hearts at clinical concentrations. The inhibition of available [CaィイD12+ィエD1]i by propofol may be mainly mediated by an impairment of sarcoplasmic reticulum CaィイD12+ィエD1 handling rather than the sarcolemmal L-type CaィイD12+ィエD1 current.