Inhibition of sodium-calcium and sodium-proton exchangers by amiloride congeners in arterial muscle cells.
The inhibitory potencies of several amiloride congeners towards Na(+)-Ca2+ and Na(+)-H+ exchange were compared in rat aortic myocytes. N-(2,4-Dimethylbenzyl)amiloride (DMB) was 10 times more potent towards Na(+)-Ca2+ than Na(+)-H+ exchange. Amiloride and ethylisopropylamiloride were about 5,000 and 10,000 times more potent toward Na(+)-H+ than Na(+)-Ca2+ exchange respectively. N-(3,4-Dichlorobenzyl)amiloride was almost equipotent towards both exchangers. About 40 nM ethylisopropylamiloride inhibited Na(+)-H+ exchange by 50%. Ethylisopropylamiloride (10 microM) had no effect on basal or angiotensin-evoked 45Ca2+ efflux or net Ca2+ efflux. In contrast to ethylisopropylamiloride, 25-50 microM DMB, which strongly inhibits Na(+)-Ca2+ exchange, markedly decreased both 45Ca2+ efflux and net Ca2+ efflux produced by angiotensin. Replacing extracellular Na+ with N-methyl-D-glucamine inhibited angiotensin-evoked 45Ca2+ efflux similarly to DMB. Neither DMB nor Na+ placement had any effect on basal or angiotensin-evoked production of [3H]inositol phosphates. These findings suggest that Na(+)-H+ exchange has no major influence on short-term Ca2+ regulation and provide evidence that Na(+)-Ca2+ exchange is a major pathway of rapid Ca2+ efflux in stimulated arterial muscle cells.
Smith
J B
JB
Department of Pharmacology, School of Medicine, University of Alabama, Birmingham 35294.
Lyu
R M
RM
Smith
L
L
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011522:Protons; D051381:Rats; D012964:Sodium / Q000378:metabolism*
D011522:Protons; D000804:Angiotensin II; D015759:Ionomycin; D000584:Amiloride; D012964:Sodium; D002118:Calcium