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百日咳毒素逆转生长抑素对精氨酸加压素诱导的环磷酸腺苷的抑制作用。

Reversal of somatostatin inhibition of AVP-induced cAMP by pertussis toxin.

作者信息

Ishikawa S, Saito T, Kuzuya T

机构信息

Department of Medicine, Jichi Medical School, Tochigi, Japan.

出版信息

Kidney Int. 1988 Feb;33(2):536-42. doi: 10.1038/ki.1988.31.

DOI:10.1038/ki.1988.31
PMID:2896265
Abstract

The effect of somatostatin on the stimulation of adenosine-3',5'-cyclic monophosphate (cAMP) production by arginine vasopressin (AVP) was examined in rat renal papillary collecting tubule cells in culture. The presence of phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine AVP at a concentration of 1 X 10(-10) M or higher significantly increased cellular cAMP levels in a dose-dependent manner. The stimulation by AVP of cellular cAMP production was significantly attenuated by 1 X 10(-6) M somatostatin (1 X 10(-9) M AVP, 477.5 +/- 23.0 vs. 292.4 +/- 28.5 fmol/micrograms protein per 10 min, P less than 0.01). When the cells were pretreated with pertussis toxin, pertussis toxin completely abolished the inhibitory effect of somatostatin on cellular cAMP production in response to AVP. Such an effect was obtained with a concentration of 0.1 ng/ml or higher of pertussis toxin and an incubation time of longer than an hour. The exposure of cells to 100 ng/ml pertussis toxin for two hours recovered the cellular cAMP response to 1 X 10(-9) M AVP in the presence of 1 X 10(-6) M somatostatin, the value of which 527.1 +/- 32.6 fmol/micrograms protein per 10 minutes, was a comparable level to that in response to only 1 X 10(-9) M AVP. Also, somatostatin inhibited the cellular cAMP response to glucagon and cholera toxin, but did not inhibit basal and forskolin-stimulated cAMP levels. Pertussis toxin treatment of cells completely abolished these inhibitory effects of somatostatin.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

在培养的大鼠肾乳头集合管细胞中,研究了生长抑素对精氨酸加压素(AVP)刺激3',5'-环磷酸腺苷(cAMP)生成的影响。磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤存在时,浓度为1×10⁻¹⁰ M或更高的AVP能以剂量依赖方式显著增加细胞内cAMP水平。1×10⁻⁶ M生长抑素能显著减弱AVP对细胞cAMP生成的刺激作用(1×10⁻⁹ M AVP时,每10分钟每微克蛋白为477.5±23.0对292.4±28.5 fmol,P<0.01)。当细胞用百日咳毒素预处理时,百日咳毒素完全消除了生长抑素对AVP诱导的细胞cAMP生成的抑制作用。浓度为0.1 ng/ml或更高的百日咳毒素以及超过1小时的孵育时间可产生这种效果。细胞在1×10⁻⁶ M生长抑素存在下,暴露于100 ng/ml百日咳毒素两小时后,对1×10⁻⁹ M AVP的细胞cAMP反应得以恢复,每10分钟每微克蛋白的值为527.1±32.6 fmol,与仅对1×10⁻⁹ M AVP的反应水平相当。此外,生长抑素抑制细胞对胰高血糖素和霍乱毒素的cAMP反应,但不抑制基础和福斯高林刺激的cAMP水平。百日咳毒素处理细胞完全消除了生长抑素的这些抑制作用。(摘要截短于250字)

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