Hypothalamic digoxin and irritable bowel syndrome.
BACKGROUND
The hypothalamus produces an endogenous membrane Na+-K+ ATPase inhibitor digoxin that can modulate neurotransmitter transport and may play a role in hemispheric dominance. It can also modulate glycoconjugate synthesis and thus affect synaptic connectivity in the bowel wall. Digoxin could play a role in the genesis of irritable bowel syndrome (IBS).


OBJECTIVE
To study digoxin status in IBS and to correlate it with hemispheric dominance.


METHODS
The isoprenoid pathway, tryptophan/tyrosine catabolic patterns and glycoconjugate metabolism were assessed in patients with IBS and in right hemispheric dominant/left hemispheric dominant/bihemispheric dominant individuals.


RESULTS
The isoprenoid pathway was upregulated in IBS, with increased HMG CoA reductase activity (0.8 [0.07] vs 0.4 [0.06] in controls; p<0.01), serum digoxin (14.8 [1.0] vs 29.0 [1.2] ng/dL; p<0.01) and dolichol levels (63.8 [3.0] vs 120.3 [3.6] mg/dL; p<0.01). RBC membrane Na+-K+ ATPase activity (3.0 [0.2] vs 1.0 [0.1] microg/p/mg protein; p<0.01), serum magnesium (1.7 [0.1] vs 1.0 [0.1] mg/dL; p<0.01) and ubiquinone (86.4 [5.9] vs 39.8 [1.2] microg/dL; p<0.01) were reduced. There was increase in tryptophan catabolites and reduction in tyrosine catabolites. Serum total glycosaminoglycan and carbohydrate component of glycoproteins were increased in IBS. The activity of glycosaminoglycan degrading enzymes and glycohydrolases were increased. This pattern correlated with those obtained in right hemispheric chemical dominance.


CONCLUSIONS
Hypothalamic digoxin and right hemispheric dominance could play a role in the genesis of irritable bowel syndrome.
Kumar
A R
AR
Department of Biochemistry, University of Kerala, Trivandrum.
Kurup
P A
PA
D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003109:Colonic Diseases, Functional / Q000097:blood*; D004077:Digoxin / Q000097:blood*; D004292:Dominance, Cerebral; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male
D015415:Biomarkers; D004077:Digoxin