In mammals, copper (Cu) absorption occurs mostly in the small intestine, and some of the Cu transporters involved in its uptake have been characterised. In fish, however, the regions of the gut involved in Cu absorption and the membrane transport mechanisms responsible for gastrointestinal Cu uptake are unknown. Everted gut sacs and isolated perfused intestine of Clarias gariepinus were used to explore Cu absorption (at 22 degrees C). Gut sacs exposed to 100 micromol l(−1) mucosal solution Cu ([Cu](m)) showed that Cu was mostly (70 %) absorbed in the middle and hind intestine. Most of the accumulated Cu was located in the mucosa. In perfused intestines, cumulative Cu absorption from the mucosal solution to the serosal perfusate was greatest at 10 micromol l(−1) [Cu](m) and decreased at higher values of [Cu](m), while tissue accumulation of Cu showed a dose-dependent elevation. Absorption efficiency therefore declined with increasing Cu dose, and basolateral transport was the limiting factor in Cu uptake. Serosal applications of the P-type ATPase inhibitor vanadate (100 micromol l(−1)) or the anion transport inhibitor DIDS (100 micromol l(−1)) caused threefold increases in net Cu uptake (at [Cu](m)=10 micromol l(−1)). The vanadate effect was explained by a reduction in transepithelial potential rather than inhibition of Cu-ATPase, but the DIDS effect was not. Transepithelial potential, water transport and tissue [Cu] were not affected by DIDS, but tissue [K(+)] was elevated. Removal of Cl(−) simultaneously from both the mucosal and serosal solutions caused a 10-fold reduction in the rate of Cu uptake, while removal of Cl(−) from the mucosal solution only completely abolished Cu absorption to the serosal perfusate. Transepithelial potential effects are discussed. We conclude that Cu absorption occurs mostly in the intestine and is normally driven by a basolateral Cu/anion symport that prefers Cl(−).

Alda
J. O.
,
Garay
R.
(
1990
).
Chloride (or bicarbonate)-dependent copper uptake through the anion exchanger in human red blood cells
.
Am. J. Physiol
259
,
570
–.
Ando
M.
(
1990
).
Effects of bicarbonate on salt and water transport across the intestine of the seawater eel
.
J. Exp. Biol
150
,
367
–.
Ando
M.
,
Kobayashi
M.
(
1978
).
Effects of stripping the outer layers of the eel intestine on salt and water transport
.
Comp. Biochem. Physiol
,
61
,
497
–.
Ando
M.
,
Sasaki
H.
,
Huang
K. C.
(
1986
).
A new technique for measuring water transport across the seawater eel intestine
.
J. Exp. Biol
122
,
257
–.
Baker
R. T. M.
,
Martin
P.
,
Davies
S. J.
(
1997
).
Ingestion of sub-lethal levels of iron sulphate by African catfish affects growth and tissue lipid peroxidation
.
Aquat. Toxicol
40
,
51
–.
Bettger
W. J.
,
Spry
D. J.
,
Cockell
K. A.
,
Cho
C. Y.
,
Hilton
J. W.
(
1987
).
The distribution of zinc and copper in plasma, erthrocytes and erthrocyte membranes of rainbow trout (Salmo gairdneri)
.
Comp. Biochem. Physiol
87
,
445
–.
Bevan
C.
,
Foulkes
E. C.
(
1989
).
Interaction of cadmium with brush border membrane vesicles from the small intestine
.
Toxicol
54
,
297
–.
Bicho
A.
,
Gil Ferreira
H.
,
Gil Ferreira
K.
(
1999
).
Chloride channels in the eel intestine
.
J. Exp. Biol
202
,
39
–.
Bijvelds
M. J. C.
,
Kolar
Z. I.
,
Wendelaar Bonga
S. E.
,
Flik
G.
(
1996
).
Magnesium transport across the basolateral membrane of fish enterocyte
.
J. Membr. Biol
154
,
217
–.
Bogdnova
A. Y.
,
Virkki
L. V.
,
Gusev
G. P.
,
Nikinmaa
M.
(
1999
).
Copper effects on ion transport across lamprey erythrocyte membrane: Cl/OH exchange induced by cuprous ions
.
Toxicol. Appl. Pharmacol
159
,
204
–.
Buckley
W. T.
(
1996
).
Application of compartmental modeling to determination of trace element requirements in humans
.
J. Nutr
126
,
2312
–.
Campbell
H. A.
,
Handy
R. D.
,
Nimmo
M.
(
1999
).
Copper uptake kinetics across the gills of rainbow trout (Oncorhynchus mykiss) measured using an improved isolated perfused head technique
.
Aquat. Toxicol
46
,
177
–.
Cantley
L. C.
,
Cantley
L. G.
,
Josephson
L.
(
1978
).
A characterization of vanadate interactions with the (Na,K)-ATPase
.
J. Biol. Chem
253
,
7361
–.
Carbonell
G.
,
Tarazona
J. V.
(
1994
).
Toxicokinetics of copper in rainbow trout (Oncorhynchus mykiss)
.
Aquat. Toxicol
29
,
213
–.
Endo
T.
,
Kimura
O.
,
Sakata
M.
(
1998
).
Cadmium uptake from apical membrane of LLC-PK1cells via inorganic anion exchanger
.
Pharmac. Toxicol
82
,
230
–.
Flonta
M. L.
,
Beir-Simaels
J.
,
De Mesotten
D.
,
Van Driessche
W.
(
1998
).
Cu2+reveals different binding sites of amiloride and CDPC on the apical Na channel of frog skin
.
Biochim. Biophys. Acta
1370
,
169
–.
Foulkes
E. C.
(
1988
).
On the mechanism of transfer of heavy metals across cell membranes
.
Toxicol
52
,
263
–.
Foulkes
E. C.
,
McMullen
D. M.
(
1987
).
Kinetics of transepithelial movement of heavy metals in rat jejunum
.
Am. J. Physiol
253
,
134
–.
Grosell
M. H.
,
Hogstrand
C.
,
Wood
C. M.
(
1997
).
Cu uptake and turnover in both Cu-acclimated and non-acclimated rainbow trout (Oncorhynchus mykiss)
.
Aquat. Toxicol
38
,
257
–.
Gunshin
H.
,
Mackenzie
B.
,
Berger
U. V.
,
Gunshin
Y.
,
Romero
M. F.
,
Boron
W. F.
,
Nussberger
S.
,
Gollan
J. L.
,
Hediger
M. A.
(
1997
).
Cloning and characterisation of a mammalian proton-coupled metal-ion transporter
.
Nature
388
,
482
–.
Handy
R. D.
,
Sims
D. W.
,
Giles
A.
,
Campbell
H. A.
,
Musonda
M. M.
(
1999
).
Metabolic trade-off between locomotion and detoxification for maintenance of blood chemistry and growth parameters by rainbow trout (Oncorhynchus mykiss) during chronic dietary exposure to copper
.
Aquat. Toxicol
47
,
23
–.
Harris
Z. L.
,
Gitlin
J. D.
(
1996
).
Genetic and molecular basis for copper toxicity
.
Am. J. Clin. Nutr
63
,
836
–.
Hartree
E. F.
(
1972
).
Determination of protein: A modification of the Lowry method gives a linear photometric response
.
Analyt. Biochem
48
,
422
–.
Jones
L. R.
,
Besch
H. R.
(
1984
).
Isolation of canine cardiac sarcolemma vesicles
.
Meth. Pharmac
5
,
1
–.
Linder
M. C.
,
Hazegh-Azam
M.
(
1996
).
Copper biochemistry and molecular biology
.
Am. J. Clin. Nutr
63
,
797
–.
Miller
T. G.
,
Mackay
W. C.
(
1982
).
Relationship of secreted mucus to copper and acid toxicity in rainbow trout
.
Bull. Env. Contam. Toxicol
28
,
68
–.
Ödblom
M. P.
,
Handy
R. D.
(
1999
).
A novel DIDS-sensitive, anion-dependent Mg2+efflux pathway in rat ventricular myocytes
.
Biochem. Biophys. Res. Commun
264
,
334
–.
Trinder
D.
,
Oates
P. S.
,
Thomas
C.
,
Sadlier
J.
,
Morgan
E. H.
(
2000
).
Localisation of divalent metal transporter 1 (DMT1) to the microvillus membrane of rat duodenal enterocytes in irondeficiency, but to hepatocytes in iron overload
.
Gut
46
,
270
–.
van Campen
D. R.
,
Mitchell
E. A.
(
1965
).
Absorption of Cu64, Zn65, Mo99and Fe59from ligated segments of the rat gastrointestinal tract
.
J. Nutr
86
,
120
–.
van der Velden
J. A.
,
Groot
J. A.
,
Flik
G.
,
Polak
P.
,
Kolar
Z. I.
(
1990
).
Magnesium transport in fish intestine
.
J. Exp. Biol
152
,
587
–.
Wapnir
R. A.
(
1991
).
Copper—sodium linkage during intestinal absorption: Inhibition by amiloride
.
Proc. Soc. Exp. Biol. Med
196
,
410
–.
Wapnir
R. A.
,
Lee
S. Y.
(
1993
).
Dietary regulation of copper absorption and storage in rats: Effects of sodium, zinc, histidine-zinc
.
J. Am. Coll. Nutr
12
,
714
–.
Wu
L.
,
Mateescu
M.
,
Wang
X.
,
Mondovi
B.
,
Wang
R.
(
1996
).
Modulation of K+channel currents by serum amineoxidase in neurons
.
Biochem. Biophys. Res. Commun
220
,
47
–.
Yoshimura
N.
(
1994
).
Histochemical localisation of copper in various organs of brindled mice
.
Path. Int
44
,
14
–.
This content is only available via PDF.