Regulation of Multiple Effectors by the Cloned δ‐Opioid Receptor: Stimulation of Phospholipase C and Type II Adenylyl Cyclase
Regulation of Multiple Effectors by the Cloned δ‐Opioid Receptor: Stimulation of Phospholipase C and Type II Adenylyl Cyclase
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克隆 δ-阿片受体对多效应器的调节：磷脂酶 C 和 II 型腺苷酸环化酶的刺激
作者：
R. Tsu;J. S. Chan;Y. Wong
摘要：δ‐阿片受体调节多种组织中的多种效应物。当在人胚胎肾293细胞中表达时，克隆的δ -阿片受体响应于δ选择性激动剂[d‐Pen2，d‐Pen5]脑啡肽抑制环AMP （cAMP）的积累。[d‐Pen2，d‐Pen5]脑啡肽的抑制作用依赖于δ -阿片受体的表达，EC50值为1 nM。该受体表现出配体选择性和适合δ -阿片亚型的药理学特征。阿片拮抗剂纳洛酮或百日咳毒素预处理细胞可阻断这种抑制作用。II型腺苷酸环化酶和αs激活突变体共同转染δ -阿片受体可将δ -阿片信号从抑制转化为刺激cAMP积累。有趣的是，当转染到Ltk−成纤维细胞时，克隆的δ‐阿片受体能够刺激肌醇磷酸的形成（EC50 = 8 nM）。这种反应对百日咳毒素敏感。阿片介导的肌醇磷酸的形成表现出与抑制cAMP积累相同的配体选择性。我们还检测了δ‐阿片受体与Gi以外的G蛋白偶联的能力。共转染研究表明，δ -阿片受体可以利用Gz调节cAMP的积累并刺激肌醇磷酸的形成。
Abstract: The δ‐opioid receptor is known to regulate multiple effectors in various tissues. When expressed in human embryonic kidney 293 cells, the cloned δ‐opioid receptor inhibited cyclic AMP (cAMP) accumulation in response to the δ‐selective agonist [d‐Pen2,d‐Pen5]enkephalin. The inhibitory response of [d‐Pen2,d‐Pen5]enkephalin was dependent on the expression of the δ‐opioid receptor and exhibited an EC50 of 1 nM. The receptor showed ligand selectivity and a pharmacological profile that is appropriate for the δ‐opioid subtype. The inhibition was blocked by the opiate antagonist naloxone or by pretreatment of the cells with pertussis toxin. Cotransfection of the δ‐opioid receptor with type II adenylyl cyclase and an activated mutant of αs converted the δ‐opioid signal from inhibition to stimulation of cAMP accumulation. It is interesting that when transfected into Ltk− fibroblasts, the cloned δ‐opioid receptor was able to stimulate the formation of inositol phosphates (EC50 = 8 nM). This response was sensitive to pertussis toxin. The opioid‐mediated formation of inositol phosphates exhibited the same ligand selectivity as seen with the inhibition of cAMP accumulation. The ability of the δ‐opioid receptor to couple to G proteins other than Gi was also examined. Cotransfection studies revealed that the δ‐opioid receptor can utilize Gz to regulate cAMP accumulation and to stimulate the formation of inositol phosphates.
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δ-阿片受体激活神经母细胞瘤 x 神经胶质瘤 NG108-15 杂交细胞中的 cAMP 磷酸二酯酶活性。
影响因子：
3.6
作者：
Law,PY;Loh,HH
通讯作者：
Loh,HH
DOI：
10.1073/pnas.90.7.2915
发表时间：
1993-04-01
影响因子：
11.1
作者：
MANGOURA, D;DAWSON, G
通讯作者：
DAWSON, G
百日咳毒素对腺苷酸环化酶的 ADP-核糖基化。
DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hsia,JA;Moss,J;Hewlett,EL;Vaughan,M
通讯作者：
Vaughan,M
血清素诱导的大鼠胃底肌肉收缩是由 G α z 样鸟嘌呤核苷酸结合蛋白介导的。
DOI：
--
发表时间：
1993
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Wang,HY;Eberle-Wang,K;Simansky,KJ;Friedman,E
通讯作者：
Friedman,E
DOI：
10.1073/pnas.90.7.3019
发表时间：
1993-04-01
影响因子：
11.1
作者：
CRUCIANI, RA;DVORKIN, B;MAKMAN, MH
通讯作者：
MAKMAN, MH