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

阿片受体刺激对完整豚鼠跳热中CaiID12+IeD1瞬变和收缩的直接影响

• 批准号: 10671434
• 负责人: MATSUMOTO Maki
• 金额: $ 1.98万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671434/
• 关键词: Intracellular CaィイD12+ィエD1 concentration; Myofilament CaィイD12+ィエD1 sensitivity; Morphine; Opioid receptor; Cardiac contractility

(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.

(1)在离体豚鼠完整跳动心脏上，应用κ-、δ-κ D21-、δ-κ D22-阿片受体拮抗剂，研究吗啡对细胞内Ca ~（2+）D_1浓度（[Ca ~（2+）D_1]i）和左心室压力（LVP）关系的影响。吗啡（1μM）可降低心肌收缩时[Ca ~（2+）D_12 + Ca ~（2+）D_1]_i，并可增强完整跳动心脏中肌丝Ca ~（2+）D_12 + Ca ~（2+）D_1的敏感性。吗啡引起的Ca ~（2+）D_1 ~（12+）D_1瞬变的减少可能主要是δ ~（2+）D_2 ~（21+）D_2 ~-和δ ~（2+）D_2 ~（22+）D_2 ~-阿片刺激所致，而不是κ阿片刺激所致。(2)δ β D21受体D2-阿片激动剂TAN-67（1μM）可降低LVP和[Ca ~（2+）D12+ Ca ~（2+）D1]i，但对LVP无影响。分别用δ α D21受体D2-和δ α D22受体D2-拮抗剂诱导心脏效应。δ β D21受体D2-和δ β D22受体D2-激动剂引起LVP发展曲线随[Ca ~（2+）D12+ Ca ~（2+）D1]i的变化而发生明显的偏移，表明这些激动剂增强了肌丝Ca ~（2+）D12+ Ca ~（2+）D1的敏感性。(3)异丙酚在不降低心脏收缩的情况下降低可用的[Ca ~（2+）D_1]i，并且在临床浓度下增强完整跳动心脏中肌丝Ca ~（2+）D_1的敏感性。异丙酚对[Ca ~（2+）D_1]i的抑制作用可能主要是通过肌浆网Ca ~（2+）D_1处理的损伤而不是肌膜L型Ca ~（2+）D_1电流介导的。

项目成果

KANAYA,N.: "Effect of isoflurane on epinephrine induced arrhythmias in ischemic-reperfused dog hearts."Res Commun Mol Pathol Pharmacol.. 100. 181-6 (1998)

KANAYA,N.：“异氟烷对缺血再灌注狗心脏中肾上腺素诱导的心律失常的影响。”Res Commun Mol Pathol Pharmacol.. 100. 181-6 (1998)

Kaneya N.: "Thiopental alters contraction,intracellular Ca^<2+>and pH in rat ventricular myocytes"Anesthesiology. 89・1. 202-214 (1998)

Kaneya N.：“硫喷妥钠改变大鼠心室肌细胞的收缩、细胞内 Ca^2+ 和 pH”麻醉学 89・1（1998）。

KANAYA,N.: "Propofol and ketamine only inhibit intracellular CaィイD12+ィエD1 transients and contraction in rat ventricular myocytes at supraclinical concentrations."Anesthesiology. 88. 781-791 (1998)

KANAYA, N.：“异丙酚和氯胺酮仅在超临床浓度下抑制大鼠心室肌细胞的细胞内 CaD12+D1 瞬变和收缩。”麻醉学。88. 781-791 (1998)

KANAYA,N.: "Thiopental alters contraction, intracellular CaィイD12+ィエD1 and pH in rat ventricular myocytes."Anesthesiology. 89. 202-214 (1998)

KANAYA, N.：“硫喷妥钠改变大鼠心室肌细胞的收缩、细胞内 CaD12+D1 和 pH 值。” 麻醉学 89. 202-214 (1998)

KANAYA.N.: "Comparative myocardial depression of sevoflurane, isoflurane and halothane in cultured neonatal rat ventricular myocytres."Anesth Analg. 87. 1041-1047 (1998)

KANAYA.N.：“七氟烷、异氟烷和氟烷对培养的新生大鼠心室肌细胞的心肌抑制作用比较。”Anesth Analg。