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 - D12+ D12 concentration（[D12+ D1]i） and left ventricular pressure (LVP) relationship in intact beating hearts isolatedfrom guinea pigs, and using specific κ-,δ D21 - D2-, δ D22 - D2-, opioid antagonists，选择刺激与直接cardiac effect of morphine . morphine （1μM）decreases available without decreasing [Ca D12+ D1]i cardiac contraction，and it enhances myofilament Ca D12+ D1 sensitivity in intact beating hearts. The decrease ofD12 transients induced by morphine would be mainly cause by δ D21 D2-，D22 -opioid stimulation，but not κ opioid stimulation.(2) δ d -opioid agonist （TAN-67, TAN-67）1μM) decreased both LVP and [Ca D12+ d D1]i，but not LVP. The cardiac effects induced by δ D21 D2-, and δ D22 D2-antagonist，respectively. The δ D21 -，d -agonists caused a leftward shift in the curve of developed LVP as a function ofavailable [Ca D12+ D1]i，这是indicated，这些agonists增强myofilament Ca - D12+ - D1 sensitivity.(3) Propofoldecreases available [Ca D12+ D1]i without decreasing cardiac contraction，and it enhances myofilament Ca D12+ D1 sensitivity in intact beating hearts at clinicalconcentrations. The inhibition of available [Ca D12+ D1]i by propofol may be mainly mediated by animpairment of sarcoplasmic reticulum Ca - D12+ D1 handling rather than the sarcolemmal -typeCa D12+ D1 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.