Pharmacological analysis by HOE642 and KB‐R9032 of the role of Na<sup>+</sup>/H<sup>+</sup> exchange in the endothelin‐1‐induced Ca<sup>2+</sup> signalling in rabbit ventricular myocytes

British Journal of Pharmacology - Tập 131 Số 3 - Trang 638-644 - 2000
Hao Wang1, Kiyoharu Sakurai1, Masao Endoh1
1Department of Pharmacology, Yamagata University School of Medicine, Yamagata 990-9585, Japan,

Tóm tắt

The role of Na+/H+ exchange in endothelin‐1 (ET‐1)‐induced increases in Ca2+ transients and cell shortening was studied in rabbit ventricular myocytes loaded with indo‐1/AM. Selective inhibitors of Na+/H+ exchange HOE642 (4‐isopropyl‐3‐methyl‐sulphonylbenzoyl guanidine methanesulphonate) and KB‐R9032 (N‐(4‐isopropyl‐2,2‐dimethyl‐3‐oxo‐3,4‐dihydro‐2H‐benzo‐[1,4]oxazine‐6‐carbonyl) guanidine methanesulphonate) were used as pharmacological tools for the analysis. ET‐1 at 0.1 nM induced an increase in Ca2+ transients by 45.6%, while it increased cell shortening by 109.6%. For a given increase in cell shortening, the ET‐1‐induced increase in Ca2+ transients was much smaller than that induced by isoprenaline (ISO, 10 nM). Pretreatment with HOE642 and KB‐R9032 (1 μM) inhibited the increase in cell shortening induced by 0.1 nM ET‐1 by 51 and 65.4%, respectively, without a significant alteration of ET‐1‐induced increase in Ca2+ transients. HOE642 and KB‐R9032 did not affect baseline levels of cell shortening and peak Ca2+ transients, and the effects of ISO (10 nM). These results indicate that activation of Na+/H+ exchange by ET‐1 may play an important role in the positive inotropic effect and the ET‐1‐induced increase in myofilament Ca2+ sensitivity in rabbit ventricular myocytes. British Journal of Pharmacology (2000) 131, 638–644; doi:10.1038/sj.bjp.0703608

Từ khóa


Tài liệu tham khảo

10.1038/361315a0

10.1113/jphysiol.1989.sp017833

10.1139/y95-242

10.1016/0306-3623(94)00144-C

10.1161/01.RES.62.2.247

10.1007/978-4-431-65952-5_25

ENDOH M., 1996, The positive inotropic effect and the hydrolysis of phosphoinositide induced by endothelin‐3 in rabbit ventricular myocardium: inhibition by a selective antagonist of ETA receptors, FR139317, J. Pharmacol. Exp. Ther., 277, 61

10.1113/jphysiol.1978.sp012231

FEDIDA D., 1993, Alpha 1‐adrenoceptors in myocardium: functional aspects and transmembrane signaling mechanisms, Physiol. Rev., 73, 469, 10.1152/physrev.1993.73.2.469

10.1016/S1071-9164(96)80058-3

10.1007/s002109900123

10.1016/0006-291X(90)90776-J

10.1161/01.RES.71.4.870

10.1016/S0021-9258(19)83641-4

10.1016/S0022-2828(08)80043-0

HU J.R., 1988, Endothelin has potent inotropic effect in rat atria, Eur. J. Pharmacol., 158, 275, 10.1016/0014-2999(88)90079-9

10.1111/j.1476-5381.1995.tb13247.x

ISHIKAWA T., 1988, Positive inotropic action of novel vasoconstrictor peptide endothelin on guinea pig atria, Am. J. Physiol., 255, H970

10.1016/0014-2999(90)94057-5

KASAI H., 1994, Pharmacological properties of endothelin receptor subtypes mediating positive inotropic effects in rabbit heart, Am. J. Physiol., 266, H2220

10.1172/JCI114822

10.1161/01.RES.68.1.269

10.1016/0008-6363(96)88573-7

MEYER M., 1996, Influence of endothelin‐1 on human atrial myocardium‐myocardial function and subcellular pathways, Basic Res. Cardiol., 91, 86, 10.1007/BF00788869

10.1016/0006-291X(89)92397-8

10.1038/334661a0

10.1161/01.RES.62.1.8

SCHOLZ W., 1995, Protective effects of HOE642, a selective sodium‐hydrogen exchange subtype 1 inhibitor, on cardiac ischaemia and reperfusion, Cardiovasc. Res., 29, 260, 10.1016/S0008-6363(96)88579-8

TAKANASHI M., 1992, Concentration‐ and time‐dependence of phosphoinositide hydrolysis induced by endothelin in relation to the positive inotropic effect in rabbit ventricular myocardium, J. Pharmacol. Exp. Ther., 262, 1189

10.1007/PL00004923

VIGNE P., 1990, Endothelin mobilizes Ca2+ from a caffeine‐ and ryanodine‐insensitive intracellular pool in rat atrial cells, J. Biol. Chem., 265, 6782, 10.1016/S0021-9258(19)39217-8

10.1161/01.RES.69.3.582

10.1007/s002109900130

10.1248/cpb.46.1716

10.1038/332411a0

10.1038/sj.bjp.0702454

10.1161/01.RES.82.10.1078

YUE D., 1987, Intracellular [Ca2+] related to rate of force development in twitch contraction of heart, Am. J. Physiol., 252, H760

Thông tin
Thông tin xuất bản

British Journal of Pharmacology

Tập 131 Số 3

638-644

Thông tin tác giả