内皮素-1_（1-31）的心血管效应及其机制研究
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摘要
ET-1_(1-31)是糜酶水解大内皮素产生的由31个氨基酸组成的内皮素家族的新成员。ET-1_(1-31)可直接激活ET受体,也可由ECE水解为ET-1_(1-21)间接产生效应。在外周,ET-1_(1-31)有收缩平滑肌、促进细胞增殖等生物学作用。ET-1_(1-31)的心血管效应尚未明确。本工作证明经冠状动脉口给予ET-1_(1-31)产生升压作用,无降压作用。中枢给予ET-1_(1-31)产生与ET-1_(1-21)类似的心血管效应,ET-1_(1-31)的中枢心血管效应通过转换为ET-1_(1-21)间接产生,不是ET-1_(1-31)本身作用。ET-1_(1-31)有增高培养心肌细胞[ca~(2+)]i的作用,10~(-8)mol/ET-1_(1-31)能减小钙瞬变幅度,该作用部分是ET-1_(1-31)的直接作用。ET-1_(1-31)的中枢心血管效应和增加胞浆[Ca~(2+)]的作用是由ETA受体介导,与ETB受体关系不大。
Abstract: ET-1_(1-31), a novel member of the endothelin family comprising 31 amino acids and derived from the selective hydrolysis of big ET-1 by chymase. Although the peripheral effects of ET--1_(1-31) have been well determined, the cardiovascular role of ET--1_(1-31) is not fully understood. Our study suggested that administration of ET--1_(1-31) through coronary artery increased blood pressure of rats. Central administration of ET--1_(1-31) produced biphasic cardiovascular effects. The central effects of ET--1_(1-31) which were mediated through ETA receptors and did nothing with ETB receptors, result from ET--1_(1-31) converting to ET--1_(1-21) ET--1_(1-31) increase [Ca~2+]I, but 10~-8 mol/L terminated [Ca~2+]I, which were partly attenuated by phosphoramidon.
Abstract: ET-1_(1-31), a novel member of the endothelin family comprising 31 amino acids and derived from the selective hydrolysis of big ET-1 by chymase. Although the peripheral effects of ET--1_(1-31) have been well determined, the cardiovascular role of ET--1_(1-31) is not fully understood. Our study suggested that administration of ET--1_(1-31) through coronary artery increased blood pressure of rats. Central administration of ET--1_(1-31) produced biphasic cardiovascular effects. The central effects of ET--1_(1-31) which were mediated through ETA receptors and did nothing with ETB receptors, result from ET--1_(1-31) converting to ET--1_(1-21) ET--1_(1-31) increase [Ca~2+]I, but 10~-8 mol/L terminated [Ca~2+]I, which were partly attenuated by phosphoramidon.
引文
1 Yanagisawa M, Kurihara H, Kimura S. et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature, 1988; 332(6163): 411-5.
2 Nakano A, Kishi F, Minami K. et al. Selective conversion of big endothelins to tracheal smooth muscle-constricting 31-amino acid-length endothelins by chymase from human mast cells. J Immunol, 1997; 159(4): 1987-92.
3 Yoshizumi M, Inui D, Kirima K. et al. Comparison of the effects of endothelin-1, -2 and -3 (1-31) on changes in [Ca2+]i in human coronary artery smooth muscle cells. Jpn J Pharmacol, 1999; 81(3): 298-304.
4 Takeji T, Nakaya Y, Kamada M. et al. Effect of a novel vasoconstrictor endothelin-1 (1-31) on human umbilical artery. Biochem Biophys Res Commun, 2000; 270(2): 622-4.
5 Saijo Y, Maeda K, Nakaya Y. et al. Altered sensitivity to a novel vasoconstrictor endothelin-1 (1-31) in myometrium and umbilical artery of women with severe preeclampsia. Biochem Biophys Res Commun, 2001; 286(5): 964-7.
6 Mazzocchi G, Rossi GP, Malendowicz LK. et al. Endothelin-1[1-31], acting as an ETA-receptor selective agonist, stimulates proliferation of cultured rat zona glomerulosa cells. FEBS Lett, 2000; 487(2): 194-8.
7 Cui P, Tani K, Kitamura H. et al. A novel bioactive 31-amino acid endothelin-1 is a potent chemotactic peptide for human neutrophils and monocytes. J Leukoc Biol, 2001; 70(2): 306-12.
8 Inui D, Yoshizumi M, Okishima N. et al. Mechanism of endothelin-1-(1-31)-induced calcium signaling in human coronary artery smooth muscle cells. Am J Physiol, 1999; 276(6 Pt 1): E1067-72.
9 Yoshizumi M, Kim S, Kagami S. et al. Effect of endothelin-1 (1-31) on extracellular signal-regulated kinase and proliferation of human coronary artery smooth muscle cells. Br J Pharmacol, 1998; 125(5): 1019-27.
10 Nagata N, Niwa Y, Nakaya Y. A novel 31-amino-acid-length endothelin, ET-1(1-31), can act as a biologically active peptide for vascular smooth muscle cells. Biochem Biophys Res Commun, 2000; 275(2): 595-600.
11 Koseki C, Imai M, Hirata Y. et al. Autoradiographic localization of [125I]-endothelin-1 binding sites in rat brain. Neurosci Res, 1989; 6(6): 581-5.
12 Kadel KA, Heistad DD, Faraci FM. Effects of endothelin on blood vessels of the brain and choroid plexus. Brain Res, 1990; 518(1-2): 78-82.
13 Matsumoto H, Suzuki N, Onda H. et al. Abundance of endothelin-3 in rat intestine, pituitary gland and brain. Biochem Biophys Res Commun, 1989; 164(1): 74-80.
14 Yamaji T, Johshita H, Ishibashi M. et al. Endothelin family in human plasma and cerebrospinal fluid. J Clin Endocrinol Metab, 1990; 71(6): 1611-5.
15 Lee ME, de la Monte SM, Ng SC. et al. Expression of the potent vasoconstrictor endothelin in the human central nervous system. J Clin Invest, 1990; 86(1): 141-7.
16 Giaid A, Gibson SJ, Ibrahim BN. et al. Endothelin 1, an endothelium-derived peptide, is expressed in neurons of the human spinal cord and dorsal root ganglia. Proc Natl Acad Sci U S A, 1989; 86(19): 7634-8.
17 Giaid A, Gibson SJ, Herrero MT. et al. Topographical localisation of endothelin mRNA and peptide immunoreactivity in neurones of the human brain. Histochemistry, 1991; 95(3): 303-14.
18 Yoshimi H, Hirata Y, Fukuda Y. et al. Regional distribution of immunoreactive endothelin in rats. Peptides, 1989; 10(4): 805-8.
19 Kohzuki M, Chai SY, Paxinos G. et al. Localization and characterization of endothelin receptor binding sites in the rat brain visualized by in vitro autoradiography. Neuroscience, 1991; 42(1): 245-60.
20 Gulati A, Rebello S. Down-regulation of endothelin receptors in the ventrolateral medulla of spontaneously hypertensive rats. Life Sci, 1991; 48(12): 1207-15.
21 Kuwaki T, Koshiya N, Takahashi H. et al. Modulatory effects of rat endothelin on central cardiovascular control in rats. Jpn J Physiol, 1990; 40(1): 977-116.
22 Ouchi Y, Kim S, Souza AC. et al. Central effect of endothelin on blood pressure in conscious rats. Am J Physiol, 1989; 256(6 Pt 2): H1747-51.
23 Kuwaki T, Kurihara H, Cao WH. et al. Physiological role of brain endothelin in the central autonomic control: from neuron to knockout mouse. Prog Neurobiol, 1997; 51(5): 545-79.
24 Kuwaki T, Cao WH, Kumada M. Endothelin in the brain and its effect on central control of the circulation and other functions. Jpn J Physiol, 1994; 44(1): 1-18.
25 Hashim MA, Tadepalli AS. Hemodynamic responses evoked by endothelin from central cardiovascular neural substrates. Am J Physiol, 1992; 262(1 Pt 2): H1-9.
26 Kuwaki T, Koshiya N, Cao WH. et al. Modulatory effects of endothelin-1 on central cardiovascular control in rats. Jpn J Physiol, 1990; 40(6): 827-41.
27 Matsumura K, Abe I, Tsuchihashi T. et al. Central effect of endothelin on neurohormonal responses in conscious rabbits. Hypertension, 1991; 17(6 Pt 2): 1192-6.
28 Rossi NF. Effect of endothelin-3 on vasopressin release in vitro and water excretion in vivo in Long-Evans rats. J Physiol, 1993; 461: 501-11.
29 Yamamoto T, Kimura T, Ota K. et al. Central effects of endothelin-1 on vasopressin release, blood pressure, and renal solute excretion. Am J Physiol, 1992; 262(6 Pt 1): E856-62.
30 Baltatu O, Nishimura H, Hoffmann S. et al. High levels of human chymase expression in the pineal and pituitary glands. Brain Res, 1997; 752(1-2): 269-78.
31 Masliniska D, Dambska M, Kaliszek A. et al. Accumulation, distribution and phenotype heterogeneity of mast cells (MC) in human brains with neurocysticercosis. Folia Neuropathol, 2001; 39(1): 7-13.
32 Paxinos G, Watson CR, Emson PC. AChE-stained horizontal sections of the rat brain in stereotaxic coordinates. J Neurosci Methods, 1980; 3(2): 129-49.
33 Rossi GP, Andreis PG, Colonna S. et al. Endothelin-1[1-31]: a novel autocrine-paracrine regulator of human adrenal cortex secretion and growth. J Clin Endocrinol Metab, 2002; 87(1): 322-8.
34 Okishima N, Yoshizumi M, Tsuchiya K. et al. Determination of the levels of novel 31-amino acid endothelins and endothelins in human lungs. Life Sci, 2001; 68(18): 2073-80.
35 Ozawa Y, Hasegawa T, Tsuchiya K. et al. Effect of endothelin-1 (1-31) on the renal resistance vessels. J Med Invest, 2003; 50(1-2): 87-94.
36 Rebuffat P, Malendowicz LK, Neri G. et al. Endothelin-1[1-31] acts as a selective ETA-receptor agonist in the rat adrenal cortex. Histol Histopathol, 2001; 16(2): 535-40.
37 Goldie RG, D'Aprile AC, Self GJ. et al. Influence of endothelin-1(1-31) on smooth muscle tone and cholinergic nerve-mediated contraction in rat isolated
2 Nakano A, Kishi F, Minami K. et al. Selective conversion of big endothelins to tracheal smooth muscle-constricting 31-amino acid-length endothelins by chymase from human mast cells. J Immunol, 1997; 159(4): 1987-92.
3 Yoshizumi M, Inui D, Kirima K. et al. Comparison of the effects of endothelin-1, -2 and -3 (1-31) on changes in [Ca2+]i in human coronary artery smooth muscle cells. Jpn J Pharmacol, 1999; 81(3): 298-304.
4 Takeji T, Nakaya Y, Kamada M. et al. Effect of a novel vasoconstrictor endothelin-1 (1-31) on human umbilical artery. Biochem Biophys Res Commun, 2000; 270(2): 622-4.
5 Saijo Y, Maeda K, Nakaya Y. et al. Altered sensitivity to a novel vasoconstrictor endothelin-1 (1-31) in myometrium and umbilical artery of women with severe preeclampsia. Biochem Biophys Res Commun, 2001; 286(5): 964-7.
6 Mazzocchi G, Rossi GP, Malendowicz LK. et al. Endothelin-1[1-31], acting as an ETA-receptor selective agonist, stimulates proliferation of cultured rat zona glomerulosa cells. FEBS Lett, 2000; 487(2): 194-8.
7 Cui P, Tani K, Kitamura H. et al. A novel bioactive 31-amino acid endothelin-1 is a potent chemotactic peptide for human neutrophils and monocytes. J Leukoc Biol, 2001; 70(2): 306-12.
8 Inui D, Yoshizumi M, Okishima N. et al. Mechanism of endothelin-1-(1-31)-induced calcium signaling in human coronary artery smooth muscle cells. Am J Physiol, 1999; 276(6 Pt 1): E1067-72.
9 Yoshizumi M, Kim S, Kagami S. et al. Effect of endothelin-1 (1-31) on extracellular signal-regulated kinase and proliferation of human coronary artery smooth muscle cells. Br J Pharmacol, 1998; 125(5): 1019-27.
10 Nagata N, Niwa Y, Nakaya Y. A novel 31-amino-acid-length endothelin, ET-1(1-31), can act as a biologically active peptide for vascular smooth muscle cells. Biochem Biophys Res Commun, 2000; 275(2): 595-600.
11 Koseki C, Imai M, Hirata Y. et al. Autoradiographic localization of [125I]-endothelin-1 binding sites in rat brain. Neurosci Res, 1989; 6(6): 581-5.
12 Kadel KA, Heistad DD, Faraci FM. Effects of endothelin on blood vessels of the brain and choroid plexus. Brain Res, 1990; 518(1-2): 78-82.
13 Matsumoto H, Suzuki N, Onda H. et al. Abundance of endothelin-3 in rat intestine, pituitary gland and brain. Biochem Biophys Res Commun, 1989; 164(1): 74-80.
14 Yamaji T, Johshita H, Ishibashi M. et al. Endothelin family in human plasma and cerebrospinal fluid. J Clin Endocrinol Metab, 1990; 71(6): 1611-5.
15 Lee ME, de la Monte SM, Ng SC. et al. Expression of the potent vasoconstrictor endothelin in the human central nervous system. J Clin Invest, 1990; 86(1): 141-7.
16 Giaid A, Gibson SJ, Ibrahim BN. et al. Endothelin 1, an endothelium-derived peptide, is expressed in neurons of the human spinal cord and dorsal root ganglia. Proc Natl Acad Sci U S A, 1989; 86(19): 7634-8.
17 Giaid A, Gibson SJ, Herrero MT. et al. Topographical localisation of endothelin mRNA and peptide immunoreactivity in neurones of the human brain. Histochemistry, 1991; 95(3): 303-14.
18 Yoshimi H, Hirata Y, Fukuda Y. et al. Regional distribution of immunoreactive endothelin in rats. Peptides, 1989; 10(4): 805-8.
19 Kohzuki M, Chai SY, Paxinos G. et al. Localization and characterization of endothelin receptor binding sites in the rat brain visualized by in vitro autoradiography. Neuroscience, 1991; 42(1): 245-60.
20 Gulati A, Rebello S. Down-regulation of endothelin receptors in the ventrolateral medulla of spontaneously hypertensive rats. Life Sci, 1991; 48(12): 1207-15.
21 Kuwaki T, Koshiya N, Takahashi H. et al. Modulatory effects of rat endothelin on central cardiovascular control in rats. Jpn J Physiol, 1990; 40(1): 977-116.
22 Ouchi Y, Kim S, Souza AC. et al. Central effect of endothelin on blood pressure in conscious rats. Am J Physiol, 1989; 256(6 Pt 2): H1747-51.
23 Kuwaki T, Kurihara H, Cao WH. et al. Physiological role of brain endothelin in the central autonomic control: from neuron to knockout mouse. Prog Neurobiol, 1997; 51(5): 545-79.
24 Kuwaki T, Cao WH, Kumada M. Endothelin in the brain and its effect on central control of the circulation and other functions. Jpn J Physiol, 1994; 44(1): 1-18.
25 Hashim MA, Tadepalli AS. Hemodynamic responses evoked by endothelin from central cardiovascular neural substrates. Am J Physiol, 1992; 262(1 Pt 2): H1-9.
26 Kuwaki T, Koshiya N, Cao WH. et al. Modulatory effects of endothelin-1 on central cardiovascular control in rats. Jpn J Physiol, 1990; 40(6): 827-41.
27 Matsumura K, Abe I, Tsuchihashi T. et al. Central effect of endothelin on neurohormonal responses in conscious rabbits. Hypertension, 1991; 17(6 Pt 2): 1192-6.
28 Rossi NF. Effect of endothelin-3 on vasopressin release in vitro and water excretion in vivo in Long-Evans rats. J Physiol, 1993; 461: 501-11.
29 Yamamoto T, Kimura T, Ota K. et al. Central effects of endothelin-1 on vasopressin release, blood pressure, and renal solute excretion. Am J Physiol, 1992; 262(6 Pt 1): E856-62.
30 Baltatu O, Nishimura H, Hoffmann S. et al. High levels of human chymase expression in the pineal and pituitary glands. Brain Res, 1997; 752(1-2): 269-78.
31 Masliniska D, Dambska M, Kaliszek A. et al. Accumulation, distribution and phenotype heterogeneity of mast cells (MC) in human brains with neurocysticercosis. Folia Neuropathol, 2001; 39(1): 7-13.
32 Paxinos G, Watson CR, Emson PC. AChE-stained horizontal sections of the rat brain in stereotaxic coordinates. J Neurosci Methods, 1980; 3(2): 129-49.
33 Rossi GP, Andreis PG, Colonna S. et al. Endothelin-1[1-31]: a novel autocrine-paracrine regulator of human adrenal cortex secretion and growth. J Clin Endocrinol Metab, 2002; 87(1): 322-8.
34 Okishima N, Yoshizumi M, Tsuchiya K. et al. Determination of the levels of novel 31-amino acid endothelins and endothelins in human lungs. Life Sci, 2001; 68(18): 2073-80.
35 Ozawa Y, Hasegawa T, Tsuchiya K. et al. Effect of endothelin-1 (1-31) on the renal resistance vessels. J Med Invest, 2003; 50(1-2): 87-94.
36 Rebuffat P, Malendowicz LK, Neri G. et al. Endothelin-1[1-31] acts as a selective ETA-receptor agonist in the rat adrenal cortex. Histol Histopathol, 2001; 16(2): 535-40.
37 Goldie RG, D'Aprile AC, Self GJ. et al. Influence of endothelin-1(1-31) on smooth muscle tone and cholinergic nerve-mediated contraction in rat isolated