Mechanisms involved in increased iron uptake across rat duodenal brush-border membrane during hypoxia.
1. Chronic hypoxia enhances intestinal iron transport but the cellular processes involved are poorly understood. In order to assess the effects of 3 days of hypoxia on iron uptake across the duodenal brush-border membrane, we have measured the membrane potential difference (Vm) of villus-attached enterocytes by direct microelectrode impalement and have used semi-quantitative autoradiography to study changes in expression of iron uptake during enterocyte maturation. 2. Hypoxia increased duodenal Vm (-57.7 vs. -49.3 mV, P < 0.001). Ion substitution experiments revealed that hyperpolarization was due, at least in part, to a reduction in brush-border Na+ permeability. 3. Autoradiography revealed that hypoxia increased by 6-fold the rate of iron accumulation during enterocyte transit along the lower villus and enhanced by 3-fold the maximal accumulation of iron. Depolarization of the brush border, using a high-K(+)-containing buffer, caused a proportionally greater reduction in iron uptake in control compared with hypoxic tissue suggesting that the raised iron uptake is only partly driven by brush-border hyperpolarization. 4. We conclude that hypoxia increases the expression of iron transport in duodenal brush-border membrane and an enhanced electrical driving force may be involved in this response.
O'Riordan
D K
DK
Department of Physiology, Royal Free Hospital School of Medicine, London, UK.
Debnam
E S
ES
Sharp
P A
PA
Simpson
R J
RJ
Taylor
E M
EM
Srai
S K
SK
D000818:Animals; D001345:Autoradiography; D004386:Duodenum / Q000098:blood supply* / Q000378:metabolism* / Q000648:ultrastructure; D006400:Hematocrit; D006454:Hemoglobins; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism; D007501:Iron / Q000032:analysis / Q000493:pharmacokinetics*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008871:Microvilli / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D006454:Hemoglobins; D007501:Iron