Park Byoung Hyun, Kim Sun Young, Kim Soo Mi, Noh Hye Jung, Cho Chong Gu, Kim Sung Zoo
Department of Internal Medicine, Medical School, Wonkwang University, Iksan, Jeonbuk 570‑749, Republic of Korea.
Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju, Jeonbuk 561‑180, Republic of Korea.
Mol Med Rep. 2015 Aug;12(2):2969-76. doi: 10.3892/mmr.2015.3678. Epub 2015 Apr 24.
Dendroaspis natriuretic peptide (DNP) shares a functionally important sequence homology with other natriuretic peptides. However, the characteristics of DNP and its receptor in the context of diabetes remafin to be fully elucidated. In the present study, alterations in the plasma levels and tissue contents of DNP and the properties of its receptor in diabetic rats, induced by streptozotocin (STZ) injection, were investigated. The plasma levels of DNP were 90.01 ± 4.12 and 196.68 ± 5.60 pg/ml in the control and STZ-induced diabetic rats, respectively. The tissue contents of DNP in the cardiac atrium, ventricle, renal cortex and inner medulla of the STZ-induced diabetic rats were also significantly increased compared with the control rats. Specific (125)I-DNP-binding sites were located predominantly in the glomeruli and inner medulla of the rat kidney. In the glomeruli of the kidney, the apparent dissociation constants (Kd) of (125)I-DNP in the control and STZ-induced diabetic rats were 0.41 ± 0.03 and 0.56 ± 0.06 nM, respectively. The maximum binding capacities (Bmax) of (125)I-DNP in control and STZ-induced diabetic rats were 2.98 ± 0.21 and 6.22 ± 1.06 fmol/mg protein, respectively. However, no differences were observed in the apparent Kd and Bmax of (125)I-DNP in the inner medulla of the kidney between the control and STZ-induced diabetic rats. In the glomerular and inner medullary kidney membranes, DNP stimulated the production of cyclic guanosine monophosphate (cGMP) in a dose-dependent manner. The magnitude of cGMP production in glomerular membranes was greater in the STZ-induced diabetic rats, whereas the magnitude of cGMP production in the inner medullary membranes was lower in the STZ-induced diabetic rats compared with the control rats. These results indicated that STZ-induced diabetes modulate DNP and its receptor, and also suggested that modulation of the DNP system is involved in the renal function of diabetic animals via the intracellular domain of the kidney NP receptor.
树眼镜蛇利钠肽（DNP）与其他利钠肽具有功能上重要的序列同源性。然而，糖尿病背景下DNP及其受体的特征仍有待充分阐明。在本研究中，对链脲佐菌素（STZ）注射诱导的糖尿病大鼠血浆中DNP水平、组织含量及其受体特性的变化进行了研究。对照组和STZ诱导的糖尿病大鼠血浆中DNP水平分别为90.01±4.12和196.68±5.60 pg/ml。与对照组大鼠相比，STZ诱导的糖尿病大鼠心房、心室、肾皮质和肾内髓质中的DNP组织含量也显著增加。特异性（125）I-DNP结合位点主要位于大鼠肾脏的肾小球和肾内髓质。在肾脏的肾小球中，对照组和STZ诱导的糖尿病大鼠中（125）I-DNP的表观解离常数（Kd）分别为0.41±0.03和0.56±0.06 nM。对照组和STZ诱导的糖尿病大鼠中（125）I-DNP的最大结合容量（Bmax）分别为2.98±0.21和6.22±1.06 fmol/mg蛋白质。然而，对照组和STZ诱导的糖尿病大鼠肾脏内髓质中（I25）I-DNP的表观Kd和Bmax未观察到差异。在肾小球和肾内髓质肾膜中，DNP以剂量依赖性方式刺激环磷酸鸟苷（cGMP）的产生。STZ诱导的糖尿病大鼠肾小球膜中cGMP产生的幅度更大，而与对照组大鼠相比，STZ诱导的糖尿病大鼠肾内髓质膜中cGMP产生的幅度更低。这些结果表明，STZ诱导的糖尿病可调节DNP及其受体，也提示DNP系统的调节通过肾脏NP受体的细胞内结构域参与糖尿病动物的肾功能。
