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心房利钠因子在肾小球和肾单位中的酶促作用及结合作用。

Enzymatic and binding effects of atrial natriuretic factor in glomeruli and nephrons.

作者信息

Kim J K, Summer S N, Durr J, Schrier R W

机构信息

Department of Medicine, University of Colorado School of Medicine, Denver.

出版信息

Kidney Int. 1989 Mar;35(3):799-805. doi: 10.1038/ki.1989.55.

Abstract

Atrial natriuretic factor (ANF) has been suggested to exert a tubular effect on the mammalian nephron, perhaps in part by interacting with other hormones. In the present study, the effect of ANF was examined on glomeruli (Gm) and different renal tubule segments including medullary (MAL) and cortical thick ascending limb (CAL) and cortical (CCT), outer medullary (OMCT) and inner medullary collecting tubules (IMCT). This effect of ANF was assessed by alteration in adenylate cyclase and cGMP in the various nephron segments in the presence and absence of arginine vasopressin (AVP), parathyroid hormone (PTH) and calcitonin (SCT). An effect of ANF (10(-8) M) was not demonstrated on adenylate cyclase (fmol cAMP formed/30 min/micrograms protein) in Gm, CAL, MAL, CCT, OMCT or IMCT. Nor did ANF (10(-8) M) interfere with the effect of PTH (5 IU/ml) on the Gm (PTH 35.1 +/- 3.7 vs. PTH + ANF 32.5 +/- 1.8, NS), CAL (PTH 50.5 +/- 10.9 vs. PTH + ANF 46.2 +/- 1.4, NS) or AVP (10(-8) M) on the CCT (AVP 40.8 +/- 6.6 vs. AVP + ANF 33.0 +/- 3.1, NS), OMCT (AVP 56.0 +/- 11.8 vs. AVP + ANF 42.1 +/- 6.7, NS), IMCT (AVP 66.5 +/- 4.6 vs. AVP + ANF 53.5 +/- 7.0, NS) or MAL (AVP 15.5 +/- 1.6 vs. AVP + ANF 14.0 +/- 2.6, NS). ANF also did not affect SCT (1.5 x 10(-8) M)-induced adenylate cyclase on CCT (SCT 69.8 +/- 11.3 vs. SCT + ANF 79.9 +/- 7.2, NS). ANF (10(-8) M), however, significantly increased cGMP in the Gm (6.4 +/- 1.7 to 121.3 +/- 32.4 fmol/micrograms protein, P less than 0.001) and IMCT (0.63 +/- 0.16 to 1.46 +/- 0.29 fmol/micrograms protein, P less than 0.05). However, no effect of ANF on cGMP was observed in the CAL, CCT, OMCT, and MAL even at 10(-7) M ANF. PTH (5 IU/ml) did not alter either basal or ANF-stimulated cGMP in the Gm. Also, specific ANF binding was studied in the microdissected IMCT. Kd was 6.08 x 10(-9) M and Bmax was 8.07 x 10(-11) M.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

心房利钠因子(ANF)被认为可能对哺乳动物肾单位产生肾小管效应,部分原因可能是与其他激素相互作用。在本研究中,检测了ANF对肾小球(Gm)和不同肾小管节段的影响,包括髓质升支粗段(MAL)、皮质升支粗段(CAL)、皮质集合管(CCT)、外髓集合管(OMCT)和内髓集合管(IMCT)。通过在有无精氨酸加压素(AVP)、甲状旁腺激素(PTH)和降钙素(SCT)的情况下,检测各肾单位节段中腺苷酸环化酶和环鸟苷酸(cGMP)的变化来评估ANF的这种作用。未发现ANF(10⁻⁸ M)对Gm、CAL、MAL、CCT、OMCT或IMCT中的腺苷酸环化酶(每分钟每微克蛋白质形成的fmol环磷酸腺苷)有影响。ANF(10⁻⁸ M)也不干扰PTH(5 IU/ml)对Gm(PTH 35.1±3.7对PTH + ANF 32.5±1.8,无显著性差异)、CAL(PTH 50.5±10.9对PTH + ANF 46.2±1.4,无显著性差异)的作用,或AVP(10⁻⁸ M)对CCT(AVP 40.8±6.6对AVP + ANF 33.0±3.1,无显著性差异)、OMCT(AVP 56.0±11.8对AVP + ANF 42.1±6.7,无显著性差异)、IMCT(AVP 66.5±4.6对AVP + ANF 53.5±7.0,无显著性差异)或MAL(AVP 15.5±1.6对AVP + ANF 14.0±2.6,无显著性差异)的作用。ANF也不影响SCT(1.5×10⁻⁸ M)诱导的CCT中腺苷酸环化酶活性(SCT 69.8±11.3对SCT + ANF 79.9±7.2,无显著性差异)。然而,ANF(10⁻⁸ M)可使Gm中的cGMP显著增加(从6.4±1.7增加到121.3±32.4 fmol/微克蛋白质,P<0.001),IMCT中的cGMP也显著增加(从0.63±0.16增加到1.46±0.29 fmol/微克蛋白质,P<0.05)。然而,即使在ANF浓度为10⁻⁷ M时,也未观察到ANF对CAL、CCT、OMCT和MAL中的cGMP有影响。PTH(5 IU/ml)对Gm中基础或ANF刺激的cGMP均无影响。此外,还研究了显微解剖的IMCT中的特异性ANF结合。解离常数(Kd)为6.08×10⁻⁹ M,最大结合容量(Bmax)为8.07×10⁻¹¹ M。(摘要截断于250字)

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