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Pharmacological studies on a novel biologically active peptide apelin produced in the adipocytes

脂肪细胞产生的新型生物活性肽apelin的药理学研究

基本信息

批准号：
11557079
负责人：
TATEMOTO Kazuhiko
金额：
$ 7.74万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11557079/
关键词：
apelin APJ arterial endothelial cells blood pressure nitric oxide hypertension arteriosclerosis eNOS オーファン受容体 NO合成阻害剤 NO合成酵素血圧サイトカイン HIV コレセプター生体防御機構エイズ感染

项目摘要

We investigated the presence of apelin and APJ transcripts and found high levels of apelin mRNA in the lung, heart, brain, ovary, intestine, and blood cells. It also presents in the adipocytes, arterial endothelial cells, gastric mucosal cells, and T cells. Apelin receptor APJ mRNA is seen in the adipocytes and arterial smooth muscle cells. The intravenous administration of apelin-12, apelin-13, and apelin-36 in the rats was found to significantly lower arterial blood pressure with no change in heart rate. Apelin-12 was more potent than apelin-13 or apelin-36 in reducing mean arterial pressure (MAP) in these rats. In contrast, apelin-9, apelin-10, and apelin-11 had no effect on MAP, suggesting that the C-terminal portion of apelin-36 with at least 12 amino acid residues may be required for its biological activity. We also examined the effects of a nitric oxide synthesis inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME), on the depressor response of apelin-12 in the rats. The administration of apelin-12 induced the decrease in MAP after apelin-12 injection in the control rats. However, the administration of the same dose of apelin-12 caused almost no change in MAP in the rats pretreated with L-NAME, indicating that the action of apelin-12 was almost completely abolished in the presence of L-NAME. We also found that apelin significantly increased plasma NOx concentrations in rats. These results suggest that the depressor response of apelin may be dependent upon the release of nitric oxide.

我们研究了apelin和APJ转录本的存在，并在肺、心脏、脑、卵巢、肠和血细胞中发现了高水平的apelin mRNA。脂肪细胞、动脉内皮细胞、胃粘膜细胞和T细胞也存在。脂肪细胞和动脉平滑肌细胞中可见apjmrna。大鼠静脉注射apelin-12、apelin-13和apelin-36可显著降低动脉血压，但心率无变化。Apelin-12在降低大鼠平均动脉压（MAP）方面比apelin-13和apelin-36更有效。相比之下，apelin-9、apelin-10和apelin-11对MAP没有影响，这表明apelin-36的c端至少有12个氨基酸残基可能是其生物活性所必需的。我们还研究了一氧化氮合成抑制剂N^ g -硝基- l -精氨酸甲酯（L-NAME）对大鼠apelin-12抑制反应的影响。注射apelin-12后，apelin-12可诱导MAP降低。然而，给药相同剂量的apelin-12对L-NAME预处理大鼠的MAP几乎没有变化，说明在L-NAME存在下，apelin-12的作用几乎完全被消除。我们还发现apelin显著增加了大鼠血浆NOx浓度。这些结果表明，apelin的抑制反应可能依赖于一氧化氮的释放。