DESENSITIZATION OF BETA-ADRENERGIC RESPONSES IN ADIPOCYTES INVOLVES RECEPTOR SUBTYPES AND CAMP-PHOSPHODIESTERASE
DESENSITIZATION OF BETA-ADRENERGIC RESPONSES IN ADIPOCYTES INVOLVES RECEPTOR SUBTYPES AND CAMP-PHOSPHODIESTERASE
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DOI：
10.1016/0922-4106(95)90100-0
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发表时间：
1995-04-28
期刊：
影响因子：
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通讯作者：
LAFONTAN, M
中科院分区：
文献类型：
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作者：
BOUSQUETMELOU, A;GALITZKY, J;LAFONTAN, M
离体脂肪细胞急性暴露于异丙肾上腺素可诱导对去甲肾上腺素和选择性β（1）-、β（2）-和β（3）-肾上腺素受体激动剂以及促肾上腺皮质激素1-24片段（ACTH）的脂解反应脱敏。毛喉素和8-溴-cAMP反应也被脱敏。当在存在OPC 3911 {N-环己基-N-2-羟乙基-4-（6-（1，2-二氢-2-氧代喹啉氧基））丁酰胺}（脂肪细胞cAMP磷酸二酯酶的特异性抑制剂）的情况下测量脂解时，所有脂解剂的脱敏作用（β（2）-肾上腺素受体激动剂除外）均被消除。异丙肾上腺素诱导膜β（1）-和β（2）-肾上腺素受体的类似损失（35%）和β（1）-肾上腺素受体的解偶联，但不改变对照β（2）-肾上腺素受体的弱偶联。这些数据表明，异丙肾上腺素诱导（i）cAMP磷酸二酯酶的激活，其仅负责去甲肾上腺素反应以及β（1）-和β（3）-肾上腺素受体介导的反应的脱敏，和（ii）唯一β（2）-肾上腺素能信号传导系统的额外脱敏，这表明调节过程的亚型选择性模式。
Acute exposure of isolated adipocytes to isoproterenol induces the desensitization of lipolytic responses to norepinephrine and selective beta(1)-, beta(2)- and beta(3)-adrenoceptor agonists, as well as the adrenocorticotropic hormone 1-24 fragment (ACTH). Forskolin and 8-bromo-cAMP responses are also desensitized. When lipolysis was measured in the presence of OPC 3911 {N-cyclohexyl-N-2-hydroxyethyl-4(6-(1,2-dihydro-2-oxoquinolyloxy))butyramide}, a specific inhibitor of the cAMP phosphodiesterase of adipocytes, the desensitization of all lipolytic agents - except the beta(2)-adrenoceptor agonist - was abolished. Isoproterenol induced a similar loss (35%) of both membrane beta(1)- and beta(2)-adrenoceptors and an uncoupling of beta(1)-adrenoceptors, but did not modify the weak coupling of control beta(2)-adrenoceptors. These data suggest that isoproterenol induced (i) an activation of the cAMP phosphodiesterase, which is solely responsible for the desensitization of norepinephrine response as well as beta(1)- and beta(3)-adrenoceptor mediated responses and (ii) an additional desensitization of the sole beta(2)-adrenergic signaling system which suggests a subtype-selective pattern of regulating processes.