D-cysteine ethyl ester and D-cystine dimethyl ester reverse the deleterious effects of morphine on arterial blood-gas chemistry and Alveolar-arterial gradient in anesthetized rats.
D-cysteine ethyl ester and D-cystine dimethyl ester reverse the deleterious effects of morphine on arterial blood-gas chemistry and Alveolar-arterial gradient in anesthetized rats.
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DOI：
10.1016/j.resp.2022.103912
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发表时间：
2022-08
影响因子：
2.3
通讯作者：
Lewis, Stephen J.
中科院分区：
文献类型：
--
作者：
Getsy, Paulina M.;Young, Alex P.;Grossfield, Alan;Seckler, James M.;Wilson, Christopher G.;Gaston, Benjamin;Bates, James N.;Lewis, Stephen J.
关键词：
我们确定了静脉注射膜渗透性兴奋剂D-半胱氨酸乙酯（（2S）-2-氨基-3-硫基丙酸乙酯）（D-CYSee）和D-胱氨酸二甲酯（（2 S）-2-氨基-3-[[（2 S）-2-氨基-3-甲氧基-3-氧代丙基]二硫烷基]丙酸甲酯）（D-CYSdime），可以克服静脉内吗啡对动脉血pH、pCO 2、pO 2和sO2以及肺泡-动脉（A-a）梯度（即，肺中气体交换的测量）。注射吗啡（2 mg/kg，IV）导致pH、pO 2和sO2显著降低，同时伴有pCO 2升高，所有这些均提示通气减少，A-a梯度升高，提示通气-灌注不匹配。随后静脉注射D-半胱氨酸乙酯（2 × 100 μmol/kg）或D-胱氨酸二甲酯（2 ×50 μmol/kg）可迅速逆转吗啡对pH、pCO 2、pO 2和sO2以及A-a梯度的负作用。类似的D-半胱氨酸注射液（2 × 100 μmol/kg，IV）没有影响，而D-胱氨酸注射液（2 × 50 μmol/kg，IV）产生了适度的逆转。我们的数据表明，D-半胱氨酸乙酯和D-胱氨酸二甲酯很容易克服吗啡对动脉血气（ABG）化学和A-a梯度的有害影响的机制，可能取决于他们的能力，迅速进入细胞。由于它们已知的进入脑、肺、胸壁肌肉以及最可能的主要外周化学感受器（即，颈动脉体），硫醇酯对吗啡引起的ABG化学和A-α梯度变化的影响可能涉及中枢和外周机制。我们正在采用目标预测方法来确定一系列体外和体内方法来测试潜在的功能蛋白，D-CYSee和D-CYSdime通过这些蛋白调节吗啡对呼吸的影响。
We determined whether intravenous injections of the membrane-permeable ventilatory stimulants, D-cysteine ethyl ester (ethyl (2 S)– 2-amino-3-sulfanylpropanoate) (D-CYSee) and D-cystine dimethyl ester (methyl (2 S)– 2-amino-3-[[(2 S)– 2-amino-3-methoxy-3-oxopropyl]disulfanyl] propanoate) (D-CYSdime), could overcome the deleterious actions of intravenous morphine on arterial blood pH, pCO2, pO2 and sO2, and Alveolar-arterial (A-a) gradient (i.e., the measure of exchange of gases in the lungs) in Sprague Dawley rats anesthetized with isoflurane. Injection of morphine (2 mg/kg, IV) caused pronounced reductions in pH, pO2 and sO2 accompanied by elevations in pCO2, all which are suggestive of diminished ventilation, and elevations in A-a gradient, which suggests a mismatch of ventilation-perfusion. Subsequent boluses of D-cysteine ethyl ester (2 × 100 μmol/kg, IV) or D-cystine dimethyl ester (2 ×50 μmol/kg, IV) rapidly reversed of the negative actions of morphine on pH, pCO2, pO2 and sO2, and A-a gradient. Similar injections of D-cysteine (2 × 100 μmol/kg, IV) were without effect, whereas injections of D-cystine (2 × 50 μmol/kg, IV) produced a modest reversal. Our data show that D-cysteine ethyl ester and D-cystine dimethyl ester readily overcome the deleterious effects of morphine on arterial blood gas (ABG) chemistry and A-a gradient by mechanisms that may depend upon their ability to rapidly enter cells. As a result of their known ability to enter the brain, lungs, muscles of the chest wall, and most likely the major peripheral chemoreceptors (i.e., carotid bodies), the effects of the thiolesters on changes in ABG chemistry and A-a gradient elicited by morphine likely involve central and peripheral mechanisms. We are employing target prediction methods to identify an array of in vitro and in vivo methods to test potential functional proteins by which D-CYSee and D-CYSdime modulate the effects of morphine on breathing.
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DOI：
10.1046/j.1440-1681.2000.03291.x
发表时间：
2000-07-01
影响因子：
2.9
作者：
Christie, MJ;Connor, M;Bagley, EE
通讯作者：
Bagley, EE
DOI：
10.1055/s-0029-1210768
发表时间：
1988-08-01
期刊：
EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY
影响因子：
--
作者：
HAUNER, H;GLATTING, G;PFEIFFER, EF
通讯作者：
PFEIFFER, EF
影响因子：
1.7
作者：
Chapman, Colin D.;Dono, Lindsey M.;Currie, Paul J.
通讯作者：
Currie, Paul J.
影响因子：
4.6
作者：
Jenkins MW;Khalid F;Baby SM;May WJ;Young AP;Bates JN;Cheng F;Seckler JM;Lewis SJ
通讯作者：
Lewis SJ
影响因子：
3.2
作者：
Jacob, C;Holme, AL;Fry, FH
通讯作者：
Fry, FH