Inhibitors of the 5-lipoxygenase arachidonic acid pathway induce ATP release and ATP-dependent organic cation transport in macrophages

SummaryTherapeutic preparations of desmopressin for parenteral use contain the preservative chlorobutanol (5 mg/ml). We show here that chlorobutanol is a potent inhibitor of platelet aggregation and release. It exhibited a significant inhibitory activity toward several aggregation inducers in a concentration- and time-dependent manner. Thromboxane B2 formation, ATP release, and elevation of cytosolic free calcium caused by collagen, ADP, epinephrine, arachidonic acid and thrombin respectively were markedly inhibited by chlorobutanol. Chlorobutanol had no effect on elastase- treated platelets and its antiplatelet effect could be reversed. It is concluded that the antiplatelet effect of chlorobutanol is mainly due to its inhibition on the arachidonic acid pathway but it is unlikely to have a nonspecitic toxic effect. This antiplatelet effect of chlorobutanol suggests that desmopressin, when administered for improving hemostasis, should not contain chlorobutanol as a preservative.

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Functional Impairment of Renal Organic Cation Transport in Experimental Diabetes

Pharmacology & Toxicology ◽

10.1034/j.1600-0773.2002.900402.x ◽

2002 ◽

Vol 90 (4) ◽

pp. 181-186 ◽

Cited By ~ 22

Author(s):

Brett Grover ◽

Christopher Auberger ◽

Rangaprasad Sarangarajan ◽

William Cacini

Keyword(s):

Functional Impairment ◽

Organic Cation ◽

Experimental Diabetes ◽

Cation Transport ◽

Organic Cation Transport

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Erratum to: Activation of liver X receptor inhibits OCT2-mediated organic cation transport in renal proximal tubular cells

Pflügers Archiv - European Journal of Physiology ◽

10.1007/s00424-017-2055-2 ◽

2017 ◽

Vol 469 (11) ◽

pp. 1483-1483

Author(s):

Teerasak Wongwan ◽

Suticha Kittayaruksakul ◽

Nithi Asavapanumas ◽

Varanuj Chatsudthipong ◽

Sunhapas Soodvilai

Keyword(s):

Organic Cation ◽

Cation Transport ◽

Liver X Receptor ◽

Organic Cation Transport ◽

Proximal Tubular Cells ◽

Tubular Cells ◽

Proximal Tubular ◽

Renal Proximal Tubular Cells ◽

Renal Proximal Tubular

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Sex-Associated Differences On The Effect Of Asa Or Flurbiprofen On Platelet Function Ex Vivo

10.1055/s-0038-1652096 ◽

1981 ◽

Author(s):

E E Nishizawa ◽

B A Molony ◽

M M Meinzinger ◽

D J Williams

Keyword(s):

Arachidonic Acid ◽

Platelet Function ◽

Bleeding Time ◽

Ex Vivo ◽

Normal Male ◽

Normal Response ◽

Beneficial Effects ◽

Acid Pathway ◽

Induced Aggregation ◽

Arachidonic Acid Pathway

It has been reported that although ASA may have some beneficial effects in males, no differences from placebo was detected in females in clinical trials on venous thrombosis, TIA and stroke. Since ASA inhibits platelet function and because the end-points measured in the above clinical studies may be related to platelet function, we measured bleeding time and platelet aggregation induced by collagen or arachidonic acid following oral administration of ASA (650 mg) or flurbiprofen (100 mg) in normal male and female volunteers (10 per group, total of 40 subjects) between the age of 50 and 70.No sex-associated differences in response with either drug were observed in bleeding time or platelet function. Thus, we were unable to confirm that the observation of beneficial effect of ASA in males was due to its effect on platelets. However, more interestingly there was a statistically shorter bleeding time in males (p = 0.026) before administration of drug. It was also found that despite the normal response to collagen, PRP prepared from pre-drug blood samples from 6 individuals (15%) did not aggregate when stimulated with arachidonic acid at concentrations as high as 1 mM. These results suggest that, at least in some individuals, collagen-induced aggregation may proceed by a pathway independent of the arachidonic acid pathway.

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Peritubular organic cation transport in isolated rabbit proximal tubules

AJP Renal Physiology ◽

10.1152/ajprenal.1994.266.3.f450 ◽

1994 ◽

Vol 266 (3) ◽

pp. F450-F458 ◽

Cited By ~ 13

Author(s):

C. E. Groves ◽

K. K. Evans ◽

W. H. Dantzler ◽

S. H. Wright

Keyword(s):

Organic Cation ◽

High Capacity ◽

Organic Cation Transporter ◽

Cation Transport ◽

Proximal Tubules ◽

Organic Cation Transport ◽

Inhibitory Potency ◽

Renal Proximal Tubules ◽

Michaelis Constants ◽

Maximal Capacity

The physiological characteristics of peritubular organic cation transport were examined by measuring the transport of the organic cation tetraethylammonium (TEA) in rabbit renal proximal tubule suspensions and isolated nonperfused rabbit renal proximal tubules. Peritubular organic cation transport in both single S2 segments and suspensions of isolated renal proximal tubules was found to be a high-capacity, high-affinity, carrier-mediated process. For tubule suspensions, the maximal capacity of the carrier for TEA (Jmax) and the concentration of TEA at 1/2 Jmax (Kt) (1.49 +/- 0.21 nmol.min-1.mg dry wt-1 and 131 +/- 16 microM, respectively), did not differ significantly from those measured in single S2 segments (Jmax, 1.16 +/- 0.075 nmol.min-1.mg dry wt-1; Kt, 108 +/- 10 microM). In addition, the pattern of inhibition of peritubular TEA transport by long-chain n-tetraalkylammonium compounds (n = 1-5) was both qualitatively and quantitatively similar in single S2 segments and tubule suspensions, exhibiting an increase in inhibitory potency with increasing alkyl chain length. For example, in tubule suspensions, apparent Michaelis constants for inhibition of TEA uptake ranged from 1.3 mM for tetramethylammonium (TMA) to 0.8 microM for tetrapentylammonium (TPeA). To determine whether these compounds were substrates for the peritubular organic cation transporter, their effect on the efflux of [14C]TEA from tubule suspensions was examined. A concentration of 0.5 mM of the short-chain tetraalkyls TMA or TEA increased the efflux of [14C]TEA (i.e., trans-stimulated) from tubules in suspension. The longer-chain tetraalkyls tetrapropylammonium, tetrabutylammonium, and TPeA all decreased the efflux of [14C]TEA from tubules in suspension; TPeA completely blocked efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

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