Mechanisms of maternofetal chloride transfer across the human placenta perfused in vitro.
To determine the relative contribution of the paracellular and transcellular routes to Cl-transfer, unidirectional maternofetal clearance (Kmf) of 36Cl was compared with Kmf of 51Cr-EDTA and creatinine across the human placenta perfused in vitro. The effect of C1-transport inhibitors 4,4'-diisothiocyanostilbene-2,2-disulfonic acid (DIDS) and diphenylamine-2-carboxylate (DPC) was also investigated. The diffusion coefficient (D) was estimated for each solute by use of an agar diffusion method. At steady state, Kmf/D for 36Cl (0.070 +/- 0.003 cm, n = 23) was not different from that for 51Cr-EDTA (0.070 +/- 0.003 cm, n = 23), and Kmf/D was significantly higher for creatinine than for 36Cl and 51Cr-EDTA (0.087 +/- 0.003 cm, n = 20, P < 0.001). Addition of the inhibitors DIDS and DPC to the perfusates resulted in a small but significant rise in Kmf of 51Cr-EDTA (0.41 +/- 0.03 vs. 0.49 +/- 0.02 ml/min, n = 16, P < 0.0001) and creatinine (0.66 +/- 0.05 vs. 0.74 +/- 0.04 ml/min, n = 13, P < 0.001), but Kmf of 36Cl was unchanged (1.11 +/- 0.07 vs. 1.13 +/- 0.05 ml/min, n = 16). There was no change in Kmf of any solute with time in control experiments. From these data, DIDS- and DPC-inhibitable fractions of Kmf for 36Cl were estimated and together accounted for 16% of total clearance. This study suggests that maternofetal flux of 36Cl across the in vitro perfused human placenta occurs predominantly, but not solely, via paracellular routes.
Doughty
I M
IM
Department of Child Health, University of Manchester, St. Mary's Hospital, United Kingdom.
Glazier
J D
JD
Greenwood
S L
SL
Boyd
R D
RD
Sibley
C P
CP
D019325:3-O-Methylglucose / Q000493:pharmacokinetics; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D002712:Chlorides / Q000493:pharmacokinetics*; D003404:Creatinine / Q000493:pharmacokinetics; D004492:Edetic Acid / Q000493:pharmacokinetics; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange; D010477:Perfusion; D010693:Phloretin / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy
D002712:Chlorides; D019325:3-O-Methylglucose; D004492:Edetic Acid; D003404:Creatinine; D005947:Glucose; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D010693:Phloretin