Sulphate conjugation of beta 2‐adrenoceptor stimulating drugs by platelet and placental phenol sulphotransferase.

Schneider, Herman

doi:10.1111/j.1365-2125.1984.tb05009.x

Cited by 9 publications

(3 citation statements)

References 6 publications

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“…The observations of stereoselective in vitro sulphate conjugation of both terbutaline and prenalterol serve to emphasize that this is also likely to occur with a number of other chiral phenolic sympathomimetic amine drugs, which also undergo sulphation in man, including salbutamol (Morgan et al, 1986), isoprenaline (Causon et al, 1984), metaproterenol (Macgregor et al, 1983), xamoterol (Marten et al, 1984), ritodrine (Brashear et al, 1988), and fenoterol (Rominger & Pollmann, 1972;Sodha & Schneider, 1984). Of these drugs enantioselective pharmacokinetics of the parent drug have been shown only for salbutamol, based on urinary data (Tan & Soldin, 1987), suggesting that the rate of sulphoconjugation may be considerably higher for the (-)than for the (+)-enantiomer, i.e.…”

Section: Discussionmentioning

confidence: 99%

Stereoselective sulphate conjugation of racemic terbutaline by human liver cytosol.

Walle

1990

Brit J Clinical Pharma

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1. The enantioselectivity of the sulphation of racemic terbutaline by phenolsulphotransferases was examined in vitro using cytosol from human livers (n = 3) and [35S]‐3′‐phosphoadenosine‐5′‐phosphosulphate (PAP35S) as the sulphate donor. 2. The radioactive sulphate conjugate formed was isolated by h.p.l.c. and its enantiomers were separated intact by h.p.l.c. after chiral derivatization. 3. Sulphation of racemic terbutaline occurred with the same apparent Km value for both enantiomers (270 microM). The extent of sulphation of the (+)‐ enantiomer was double that of the (‐)‐enantiomer, solely due to a difference in their apparent Vmax values. 4. Sulphation of racemic prenalterol, a structural analogue of terbutaline, also showed a two‐ fold preference for the (+)‐enantiomer. 5. These findings suggest that enantioselective sulphate conjugation of chiral phenolic sympathomimetic amine drugs may lead to enantioselective pharmacokinetics that should be considered in the clinical use of these drugs.

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Section: Discussionmentioning

confidence: 99%

Stereoselective sulphate conjugation of racemic terbutaline by human liver cytosol.

Walle

1990

Brit J Clinical Pharma

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“…The placenta has the capacity of promoting elimination of drugs and natural substances by sulfation (Sodha and Schneider, 1984, Stanley et al, 2001). Since sulfate metabolites bear a negative charge at physiological pH it is likely that passive diffusion would not be the predominant mechanism of their elimination out of the placenta.…”

Section: Introductionmentioning

confidence: 99%

MRP isoforms and BCRP mediate sulfate conjugate efflux out of BeWo cells

Mitra

Audus

2010

International Journal of Pharmaceutics

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The breast cancer resistance protein (BCRP) and the multidrug resistance-associated proteins (MRPs) have the ability to eliminate sulfate conjugates but it is not known if this constitutes one of their roles in the placenta. To determine this, the BeWo cell line was used as a model of placental trophoblast cells and we examined the mechanisms of elimination of two common sulfotransferase substrates, 4-nitrophenol and acetaminophen. At 0.5-200 μM, neither 4-nitrophenyl sulfate nor acetaminophen sulfate affected the accumulation of the BCRP substrates BODIPY FL prazosin or mitoxantrone in BeWo monolayers, indicating a lack of interaction of BCRP with the sulfates. Efflux studies and bidirectional transport studies examining the effect of BCRP/MRP inhibitors on the efflux of intracellularly generated 4-nitrophenyl sulfate and acetaminophen sulfate, indicated that one or more of the MRP isoforms play a major role in the elimination of 4-nitrophenyl sulfate and acetaminophen sulfate across the basolateral (fetal-facing) and apical (maternal-facing) membranes respectively. BCRP played a minor role in the elimination of these two sulfate conjugates across the apical membrane. Our study shows that a yet undetermined role of trophoblast efflux transporters is the elimination of sulfate conjugates.

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“…Sulfation of medicinal drugs has been detected, and subsequently several sulfotransferase isoforms have been identified in term and mid-gestation human placenta [12, 13]. Examination of placental tissue sections (of both maternal and fetal origin) revealed that the phenolic sulfotransferase isoforms SULT1A1 and SULT1A3 were functional in all sections.…”

Section: Introductionmentioning

confidence: 99%

Expression and functional activities of selected sulfotransferase isoforms in BeWo cells and primary cytotrophoblast cells

Mitra

Audus

2009

Biochemical Pharmacology

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Several cytosolic sulfotransferase enzyme isoforms are functional in placenta but there is limited information available on the utility of cultured trophoblast cells for studying sulfation. The trophoblast cell layer constitutes the rate-determining barrier for trans-placental transfer. The objective of this work was to examine the mRNA expression and enzyme activities of four sulfotransferase isoforms reported to be functional in human placenta (SULT1A1, SULT1A3, SULT1E1, and SULT2A1) in primary cytotrophoblast cells and the trophoblast-like BeWo cell line. Reverse transcription polymerase chain reaction (RT-PCR) was performed to determine mRNA expression. Enzyme activities were assessed using the following substrates: 4-nitrophenol for SULT1A1, dopamine for SULT1A3, 17β-estradiol for SULT1E1, and dehydroepiandrosterone for SULT2A1. For 4-nitrophenol and dopamine sulfation, apparent Km values, response to inhibitors (2,6-dichloro-4-nitrophenol and sodium chloride), and thermal stability profiles indicated that 4-nitrophenol and dopamine sulfation in BeWo cells were being mediated by SULT1A1 and SULT1A3, respectively. SULT1A1 and SULT1A3 were also functional in the cytotrophoblast cells. Both at the protein and at the mRNA levels, SULT1A1 was more abundant in BeWo cells in comparison to the primary cytotrophoblast cells. SULT1E1 and SULT2A1 mRNA were not detected in the cytotrophoblasts. SULT1E1 mRNA was weakly expressed in BeWo but there was negligible functional activity. Although SULT2A1 mRNA was abundantly expressed in BeWo, Western blot and enzyme activities revealed that the protein is not expressed in BeWo cells. The results suggest that the BeWo cells and the cytotrophoblast cells can be used to examine the roles of SULT1A1 and SULT1A3 in placental metabolism.

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Sulphate conjugation of beta 2‐adrenoceptor stimulating drugs by platelet and placental phenol sulphotransferase.

Cited by 9 publications

References 6 publications

Stereoselective sulphate conjugation of racemic terbutaline by human liver cytosol.

Stereoselective sulphate conjugation of racemic terbutaline by human liver cytosol.

MRP isoforms and BCRP mediate sulfate conjugate efflux out of BeWo cells

Expression and functional activities of selected sulfotransferase isoforms in BeWo cells and primary cytotrophoblast cells

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