Molecular and functional studies of electrogenic Na(+) transport in the distal colon and rectum of young and elderly subjects.
BACKGROUND
Human distal nephron and distal colon both exhibit mineralocorticoid sensitive electrogenic Na(+) absorption and make significant contributions to Na(+) homeostasis. Na(+) resorption in the distal nephron diminishes with age but it is unclear whether a similar change occurs in the distal colon.


OBJECTIVE
To evaluate the effect of age on expression of apical Na(+) channels and basolateral Na(+), K(+)-ATPase, and on the responsiveness of electrogenic Na(+) absorption to mineralocorticoid stimulation in human distal colon and rectum.


METHODS
Mucosal biopsies were obtained from healthy sigmoid colon and proximal rectum in "young" (aged 20-40 years) and "old" (aged 70 years or over) patients during routine colonoscopy/flexible sigmoidoscopy. Na(+) channel subunits and Na(+), K(+)-ATPase isoforms were studied at the mRNA level by in situ hybridisation and northern blotting, and at the protein level by immunocytochemistry and western blotting. The mineralocorticoid responsiveness of electrogenic Na(+) absorption was evaluated in the two groups by measuring amiloride sensitive electrical potential difference (PD) in the proximal rectum before and 24 hours after oral administration of 1 mg of fludrocortisone.


RESULTS
Na(+) channel subunit and Na(+), K(+)-ATPase isoform expression at the level of mRNA and protein was similar in "young" and "old" patients. Both basal and the fludrocortisone stimulated amiloride sensitive rectal PDs were similar in the two groups.


CONCLUSIONS
In contrast with the distal nephron, mineralocorticoid sensitive electrogenic Na(+) absorption in the human distal colon does not diminish with age, and may be particularly important in maintaining Na(+) homeostasis in the elderly.
Department of Medicine, University of Manchester, Hope Hospital, Salford, Manchester, UK.
E R
ER
Greig
T
T
Mathialahan
R P
RP
Boot-Handford
G I
GI
Sandle
D000042:Absorption / Q000502:physiology; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D000584:Amiloride / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D005438:Fludrocortisone / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D017136:Ion Transport / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D012007:Rectum / Q000378:metabolism* / Q000473:pathology; D015222:Sodium Channels / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D012333:RNA, Messenger; D015222:Sodium Channels; D000584:Amiloride; D000254:Sodium-Potassium-Exchanging ATPase; D005438:Fludrocortisone