AT(1) RECEPTORS MEDIATE THE RELEASE OF PROSTAGLANDINS IN PORCINE SMOOTH-MUSCLE CELLS AND RAT ASTROCYTES

被引：39

作者：

LEUNG, KH ^{[1
]}

CHANG, RSL ^{[1
]}

LOTTI, VJ ^{[1
]}

ROSCOE, WA ^{[1
]}

SMITH, RD ^{[1
]}

TIMMERMANS, PBMWM ^{[1
]}

CHIU, AT ^{[1
]}

机构：

[1] DUPONT MERCK PHARMACEUT CO,POB 80400,WILMINGTON,DE 19880

来源：

AMERICAN JOURNAL OF HYPERTENSION | 1992年 / 5卷 / 09期

关键词：

PROSTACYCLIN; PROSTAGLANDIN-E2; THROMBOXANE-A2; ANGIOTENSIN RECEPTOR ANTAGONIST; LOSARTAN; ANGIOTENSIN-II; PD123177;

D O I：

10.1093/ajh/5.9.648

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

Angiotensin II (AII) can release arachidonic acid metabolites such as prostacyclin (PGI2) and PGE2 from cells in cultures. It has recently been reported that the AT1 selective nonpeptide AII receptor antagonist losartan had similar effects. The present study was undertaken to further evaluate the effects of AII and losartan on cells which synthesize prostaglandins, including vascular smooth muscle, endothelial, and glial cells. Inhibition of specific [I-125]AII binding was demonstrated in porcine smooth muscle cell (PSMC) suspensions with unlabeled AII and losartan. The IC50 values were 1.3 X 10(-9) mol/L and 7.7 X 10(-9) mol/L, respectively. PD123177 (an AT2 selective antagonist) had no effect on binding. AII produced a concentration-related increase in calcium mobilization (fura-2 fluorescence) which was blocked by losartan (IC50 = 8.4 X 10(-8) mol/L) but not by PD123177 (10(-6) mol/L). AII (10(-7) to 10(-5) mol/L) stimulated the basal release of PGI2 by 100%. This response was blocked by losartan (10(-6) to 10(-5) mol/L) but not by PD123177 (10(-6) to 10(-5) mol/L) and neither agent stimulated basal release in PSMC. Similar effects of All and antagonists were observed upon receptor binding and PGE2 release in primary rat astrocyte (RA) cultures. All did not release PGI2 from porcine endothelial cells, bovine pulmonary arterial endothelial cells, or rat C6 glioma cells. Losartan had no significant effect at 10(-5) mol/L. By contrast, bradykinin or the calcium ionophore A23187 dramatically increased PGI2 release in each of these cells. AII did not release either PGI2 or thromboxane A2 from rat spleen macrophages which were responsive to A23187. Losartan and PD123177 had no effect at 10(-5) mol/L. It is concluded that AII release of prostacyclin is cell type specific. The AII-induced PGI2 and PGE2 release in PSMC and RA, respectively, is AT1 receptor subtype mediated. Losartan had no effect on the release of arachidonic acid metabolites.

引用

页码：648 / 656

页数：9

共 30 条

[1]

Gunther S., Characterization of angiotensin II receptor subtypes in rat liver, J Biol Chem, 259, pp. 7622-7629, (1984)

[2]

Peach M.J., Pharmacology of angiotensin II, Kidney Horm, 3, pp. 273-308, (1986)

[3]

Chiu A.T., Herblin W.F., McCall D.E., Et al., Identification of angiotensin II receptor subtypes, Biochem Biophys Res Commun, 165, pp. 196-203, (1989)

[4]

Chiu A.T., McCall D.E., Price W.A., Et al., Nonpeptide angiotensin II receptor antagonists. VII. Cellular and biochemical pharmacology of DuP 753, an orally active antihypertensive agent, J Pharmacol Exp Ther, 252, pp. 711-718, (1990)

[5]

Chang R., Lotti V.L., Two distinct angiotensin II receptor binding sites in rat adrenal revealed by new selective nonpeptide ligands, Molec Pharmacol, 29, pp. 347-351, (1990)

[6]

Leung K.H., Smith R.D., Timmermans P., Chiu A.T., Regional distribution of the two subtypes of angiotensin II receptor in rat brain using selective nonpeptide antagonists, Neurosci Lett, 123, pp. 95-98, (1991)

[7]

Bumpus F.M., Catt K.J., Chiu A.T., Et al., Nomenclature for angiotensin receptors, Hypertension, 17, pp. 720-721, (1991)

[8]

Moncada S., Vane J.R., Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2 and prostacyclin, Pharmacol Rev, 30, pp. 293-331, (1979)

[9]

Samuelsson B., Borgeat P., Hammerstrom S., Murphy R.C., Leukotrienes: A new group of biologically active compounds, Adv Prostaglandin Thromboxane Leukotriene Res, 6, pp. 1-18, (1980)

[10]

Mistry M., Nasjletti A., Role of pressor prostanoids in rats with angiotensin Il-salt-induced hypertension, Hypertension, 11, pp. 758-762, (1988)

← 1 2 3 →