A kinetic analysis of drugs that inhibit the adrenergic neuronal membrane amine pump

Effects of Na+ and K+ on the uptake of metaraminol by rabbit ventricular slices

“…These ionic requirements are similar to those of the Na+ and K+ activated membrane ATPase (Skou, 1965) providing further evidence for the suggested role of the membrane ATPase in catecholamine transport (Berti & Shore, 1967;.…”

Cation and Metabolic Requirements for Retention of Metaraminol by Rat Uterine Horns

“…Thus in both cases retention is dependent on Na+ and K+ and energy supplies; previous studies have shown that retention of both amines is dependent on an intact adrenergic innervation, results in concentration of the amine and is inhibited by ouabain, reduced temperatures and a number of compounds (Giachetti & Shore, 1966;Berti & Shore, 1967). As indicated earlier, however, a marked difference is seen when retention of the two amines is compared in tissues pretreated with reserpine; retention of metaraminol is normal whereas that of noradrenaline is greatly reduced (Giachetti & Shore, 1966).…”

“…This is indicated by the observations that ouabain prevents amine retention (Dengler, 1965;Green & Miller, 1966a), that the action of various digitalis-like compounds on metaraminol retention seems to be proportional to inhibition of the Na+-K+ dependent adenosine triphosphatase (ATPase) (Berti & Shore, 1967), that omitting Na+ or K+ from the medium inhibits amine retention (Iversen & Kravitz, 1966;Gillis & Paton, 1966Paton, 1967) and that an increase in K+ concentration in the external medium overcomes the reduction in amine retention induced by ouabain (Titus & Dengler, 1966). The exact nature of the relationship between amine and cation transport is unknown.…”

Pharmacological properties of centrally administered ouabain and their modification by other drugs

“…Recently, Ebadi & Carver (1970) have shown that chlorprothixene has similar effects in the rat brain. These observations, together with the knowledge that the reuptake of neuronally released catecholamines is inhibited by blockade of the sodium pump (Berti & Shore, 1967), suggest that the pharmacological effects of intracerebroventricular ouabain may be brought about by an interference with amine reuptake in the brain. However, such a theory is difficult to reconcile with the anti-ouabain effects of desmethylimipramine unless, because of its peripheral (subcutaneous) administration, the latter exerts its anti-ouabain effects at another site.…”

“…Intravenous doses of ouabain up to 10 ptg and subcutaneous doses up to 20 Lg per mouse produced no signs of central nervous depression; occasionally, the largest doses produced a small degree of hypothermia (up to 3°C at 30 min). Effects of intracerebroventricular ouabain on whole brain amine concentrations There have been several reports that both in vitro and in vivo, ouabain may interfere with the synthesis (Anagnoste & Goldstein, 1967;Goldstein, Ohi & Backstrom, 1970) and uptake (Berti & Shore, 1967;Blackburn, French & Merrills, 1967;Bogdanski, Tissari & Brodie, 1968) of catecholamines and indolealkylamines. Consequently, the effects of intracerebroventricular ouabain on whole brain amine concentrations were investigated in an attempt to explain some of the observed pharmacological effects of intracerebroventricular ouabain, described above.…”