Inhibitory and Stimulatory Effects of Amiloride Analogues on Sodium Transport in Frog Skin

Overview

Journal J Membr Biol

Date 1979 Apr 20

PMID 448731

Citations 10

Authors

J H Li

R C de Sousa

Affiliations

Soon will be listed here.

Abstract

Effects of amiloride analogues on Na transport were studied in isolated skins of the frog Rana ridibunda. The pattern of structure-activity relationship of these compounds showed that both the -NH2 group at position 5 and Cl at position 6 of the pyrazine ring of the amiloride molecule were important for their biological activity. The paramount role of the groups at position 5 was further demonstrated by the striking properties of an analogue resulting from dimethylation of that -NH2 group. A stimulation of Na transport, opposite to the effect of amiloride itself, was observed in this instance. The increase in Na transport could already be seen at 10(-6) M and was equivalent to the measured increase in Na influx, reversible, dose-dependent, and additive to the natriferic action of oxytocin. Such characteristics resemble those reported with "external" agents like propranolol and La3+. Furthermore, mutual inhibition was observed between the stimulatory effects of this analogue and those of propranolol or La3+. These results suggest that the analogue may be considered as another "external" agent acting at sites of the external membrane distinct from those activated by cAMP but similar to the Ca sites described by Herrera and Curran (Herrera, F.C., Curran, P.F. 1963. J. Gen. Physiol. 46:999).

Citing Articles

Control of sodium permeability of the outer barrier in toad skin.

Bevevino L, Lacaz-Vieira F J Membr Biol. 1982; 66(2):97-107.

PMID: 6804631 DOI: 10.1007/BF01868486.

Chemical stimulation of Na transport through amiloride-blockable channels of frog skin epithelium.

Li J, Lindemann B J Membr Biol. 1983; 75(3):179-92.

PMID: 6313927 DOI: 10.1007/BF01871949.

Poorly selective cation channels in the skin of the larval frog (stage less than or equal to XIX).

Hillyard S, Zeiske W, Van Driessche W Pflugers Arch. 1982; 394(4):287-93.

PMID: 6292822 DOI: 10.1007/BF00583692.

Inhibition of amiloride-sensitive sodium conductance by indoleamines.

Legris G, Will P, Hopfer U Proc Natl Acad Sci U S A. 1982; 79(6):2046-50.

PMID: 6281791 PMC: 346119. DOI: 10.1073/pnas.79.6.2046.

Sodium flux in the apical membrane of the toad skin: aspects of its regulation and the importance of the ionic strength of the outer solution upon the reversibility of amiloride inhibition.

Lacaz-Vieira F J Membr Biol. 1986; 92(1):27-36.

PMID: 3091839 DOI: 10.1007/BF01869013.

References

Cuthbert A . An upper limit to the number of sodium channels in frog skin epithelium. J Physiol. 1973; 228(3):681-92. PMC: 1331246. DOI: 10.1113/jphysiol.1973.sp010106. View

Li J, DESOUSA R, Essig A . Kinetics of tracer flows and isotope interaction in an ion exchange membrane. J Membr Biol. 1974; 19(1):93-104. DOI: 10.1007/BF01869972. View

Porzig H . Comparative study of the effects of propranolol and tetracaine on cation movements in resealed human red cell ghosts. J Physiol. 1975; 249(1):27-49. PMC: 1309556. DOI: 10.1113/jphysiol.1975.sp011001. View

Singer M . Effects of amiloride and dibucaine on a model phospholipid membrane--structure-activity relationships. Biochem Pharmacol. 1974; 23(21):2939-50. DOI: 10.1016/0006-2952(74)90268-8. View

Curran P, Herrera F, FLANIGAN W . The effect of Ca and antidiuretic hormone on Na transport across frog skin. II. Sites and mechanisms of action. J Gen Physiol. 1963; 46:1011-27. PMC: 2195298. DOI: 10.1085/jgp.46.5.1011. View

Nagel W . Intercellular junctions of frog skin epithelial cells. Nature. 1976; 264(5585):469-71. DOI: 10.1038/264469a0. View

Li J, de Sousa R . Effects of Ag+ on frog skin: interactions with oxytocin, amiloride and ouabain. Experientia. 1977; 33(4):433-6. DOI: 10.1007/BF01922195. View

Sudou K, Hoshi T . Mode of action of amiloride in toad urinary bladder. An electrophysiological study of the drug action on sodium permeability of the mucosal border. J Membr Biol. 1977; 32(1-2):115-32. DOI: 10.1007/BF01905212. View

. Stimulation of sodium transport in frog skin by 2-imidazolines (guanidinbenzimidazole and phentolamine). Life Sci. 1974; 15(3):539-42. DOI: 10.1016/0024-3205(74)90351-8. View

10.

Lindemann B, Van Driessche W . Sodium-specific membrane channels of frog skin are pores: current fluctuations reveal high turnover. Science. 1977; 195(4275):292-4. DOI: 10.1126/science.299785. View

11.

Cuthbert A, Maetz J . Amiloride and sodium fluxes across fish gills in fresh water and in sea water. Comp Biochem Physiol A Comp Physiol. 1972; 43(1):227-32. DOI: 10.1016/0300-9629(72)90487-2. View

12.

Cragoe Jr E, WOLTERSDORF Jr O, BICKING J, KWONG S, Jones J . Pyrazine diuretics. II. N-amidino-3-amino-5-substituted 6-halopyrazinecarboxamides. J Med Chem. 1967; 10(1):66-75. DOI: 10.1021/jm00313a014. View

13.

Benos D, Simon S, Mandel L, Cala P . Effect of amiloride and some of its analogues of cation transport in isolated frog skin and thin lipid membranes. J Gen Physiol. 1976; 68(1):43-63. PMC: 2228413. DOI: 10.1085/jgp.68.1.43. View

14.

Riddle T, Mandel L, Goldner M . Dilantin-calcium interaction and active Na transport in frog skin. Eur J Pharmacol. 1975; 33(1):189-92. DOI: 10.1016/0014-2999(75)90155-7. View

15.

Herrera F, Curran P . The effect of Ca and antidiuretic hormone on Na transport across frog skin. I. Examination of interrelationships between Ca and hormone. J Gen Physiol. 1963; 46:999-1010. PMC: 2195312. DOI: 10.1085/jgp.46.5.999. View

16.

de Sousa R, Grosso A . Vasopressin-like effects of a hallucinogenic drug--harmaline--on sodium and water transport. J Membr Biol. 1978; 40(1):77-94. DOI: 10.1007/BF01909740. View

17.

Curran P, GILL Jr J . The effect of calcium on sodium transport by frog skin. J Gen Physiol. 1962; 45:625-41. PMC: 2195197. DOI: 10.1085/jgp.45.4.625. View

18.

Grosso A, de Sousa R . Vasopressin-like effects of psychotropic drugs in amphibian epithelia. J Membr Biol. 1978; 40 Spec No:305-21. DOI: 10.1007/BF02026013. View

19.

Zeiske W, Lindemann B . Chemical stimulation of Na + current through the outer surface of frog skin epithelium. Biochim Biophys Acta. 1974; 352(2):323-6. DOI: 10.1016/0005-2736(74)90223-5. View

20.

McCLANE T . A BIPHASIC ACTION OF OUABAIN ON SODIUM TRANSPORT IN THE TOAD BLADDER. J Pharmacol Exp Ther. 1965; 148:106-10. View