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Arzneimittelforschung. 1978;28(7):1105-11.
1,4-Dimorpholino-7-phenylpyrido[3,4-d]pyridazine (SD-511) as a new type of diuretic agent.

Inada Y, Shibouta Y, Shimakawa H, Nishikawa K, Kikuchi S.

Diuretic features of 1,4-dimorpholino-7-phenylpyrido[3,4-d]pyridazine (DS-511) were studied in rats and mice. DS-511 was similar in diuretic effect to that of hydrochlorothiazide (HC) in both species, but was more water diuretic and less potassium-releasing than HC. After oral administration of DS-511 to rats the diuretic effect promptly appeared and lasted for 4 to 5 h. These patterns on onset and duration were similar to those of furosemide and acetazolamide (AZ). DS-511 was effective in experimentally induced acidotic and alkalotic rats. When DS-511 was used in combinations with other diuretics such as HC, AZ and triamterene at their maximum effective doses, urine volume and sodium excretion further increased, but potassium did not. Diuretic activity of DS-511 was not reduced by daily oral administration for 10 days to rats. In rats DS-511 reversed antidiuretic hormone (ADH)-induced antidiuresis. These findings suggest that DS-511 differs in mode and/or site of action from the known diuretics.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=582697&dopt=Abstract

Perit Dial Int. 1993;13(3):201-7.
In vitro study of the mechanism of potassium transport into human mesothelial cells. I: Effect of hyperosmolality.

Breborowicz A, Witowski J, Knapowski J, Serkes KD, Martis L, Oreopoulos DG.

Department of Pathophysiology, Medical Academy Poznan, Poland.

OBJECTIVE: To study the mechanism(s) of potassium transport into human mesothelial cells (HMC) exposed to osmotic solutes. DESIGN: Using potassium analog 86Rb, we evaluated its intracellular transport through three pathways: 1. blocked by ouabain; 2. blocked by furosemide but not by ouabain; 3. blocked by neither furosemide nor ouabain. Experiments were performed in a normotonic medium (control) or in a medium supplemented with osmotic solutes (glucose, glycerol, mannitol). Both the acute and chronic effects of osmotic solutes on potassium transport were studied. RESULTS: The acute exposure of mesothelial cells to osmotic solutes modifies the intracellular transport of potassium through all studied channels, and the effect is specific for every solute. In mesothelial cells exposed over 7 days to glucose (90 mM), the intracellular transport via ouabain- and furosemide-blocked channels is decreased, whereas it is increased through the third pathway. Total intracellular accumulation of 86Rb (potassium) ions in mesothelial cells cultured in a medium supplemented with various concentrations of glucose is decreased, and this effect is proportional to the concentration of glucose in the medium. CONCLUSIONS: The intracellular transport of potassium in mesothelial cells is regulated through at least three independent mechanisms. Acute or chronic exposure of mesothelial cells to a hypertonic medium affects the intracellular accumulation of potassium, and this effect is specific for the various osmotic solutes.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8369350&dopt=Abstract

aub.edu.lb

This work provides substantial evidence for the advocated diuretic effect of parsley in folk medicine and determines the mechanism of action of the herb. Rats offered an aqueous parsley seed extract to drink, eliminated a significantly larger volume of urine per 24 h as compared to when they were drinking water. These findings were supported by the results of other experiments using an in situ kidney perfusion technique which demonstrated also a significant increase in urine flow rate with parsley seed extract. This effect was still apparent in presence of amiloride, furosemide and in the absence of sodium, but not in the absence of potassium, suggesting that the diuretic effect of the herb is mediated through an increase in K+ retention in the lumen. Parsley extract, was shown on the other hand, to reduce the activity of the Na+-K+ ATPase in both cortex and medulla homogenates. Such an inhibition would decrease apical cellular Na+ reabsorption, lower K+ secretion, increase K+ concentration in the intercellular space and consequently would inhibit passive K+ influx across the tight junctions. The mechanism of action of parsley seems to be mediated through an inhibition of the Na+-K+ pump that would lead to a reduction in Na+ and K+ reabsorption leading thus to an osmotic water flow into the lumen, and diuresis.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11849841&dopt=Abstract

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