Saavedra J M, Kurihara M
Section on Pharmacology, National Institute of Mental Health, Bethesda, MD 20892-0999.
Can J Physiol Pharmacol. 1991 Oct;69(10):1567-75. doi: 10.1139/y91-233.
Quantitative autoradiography was used to localize and characterize atrial natriuretic peptide (ANP) receptors in the rat brain and to study their regulation. Peptide receptors are selectively located to circumventricular organs outside the blood brain barrier, such as the subfornical organ, and to brain areas involved in fluid and cardiovascular regulation. Dehydration, either by water deprivation of normal rats, or chronic dehydration present in homozygous Brattleboro rats lacking vasopressin, results in large increases in ANP binding in receptor number in the subfornical organ. In the deoxycorticosterone acetate (DOCA)-salt hypertensive model, only salt treatment, but not DOCA alone or the combination of DOCA-salt, increased the ANP receptor number in the subfornical organ and the choroid plexus. Both young and adult genetically hypertensive rats have a greatly decreased ANP receptor number in the subfornical organ and the choroid plexus. Selective displacement with an inactive analog lacking the disulfide bond (ANP 111-126) suggests that genetically hypertensive rats may lack C (clearance) atrial natriuretic peptide receptors. Our results implicate brain atrial natriuretic peptide receptors in the central response to alterations in fluid regulation and blood pressure.
采用定量放射自显影技术定位并鉴定大鼠脑中的心钠素(ANP)受体,并研究其调节机制。肽受体选择性地定位于血脑屏障外的室周器官,如穹窿下器官,以及参与液体和心血管调节的脑区。无论是正常大鼠限水导致的脱水,还是缺乏抗利尿激素的纯合布拉特洛维大鼠存在的慢性脱水,都会使穹窿下器官中ANP结合及受体数量大幅增加。在醋酸脱氧皮质酮(DOCA)-盐高血压模型中,只有盐处理能增加穹窿下器官和脉络丛中的ANP受体数量,单独使用DOCA或DOCA与盐联合使用则无此作用。幼年和成年遗传性高血压大鼠穹窿下器官和脉络丛中的ANP受体数量均大幅减少。用缺乏二硫键的无活性类似物(ANP 111-126)进行选择性置换表明,遗传性高血压大鼠可能缺乏C(清除)型心钠素受体。我们的研究结果表明,脑心钠素受体参与了对液体调节和血压改变的中枢反应。