Glucose uptake in enterocytes: a test for molecular targets of okadaic acid.
The main diarrheic shellfish poisoning (DSP) toxin is okadaic acid (OA). Although OA is a protein phosphatase 1 and 2A inhibitor less is known about the involvement of the toxin in diarrhea. The initial statement was that OA, by altering the phosphorylation state of proteins, might modify glucose uptake and consequently ionic and water reabsorption across the small intestine. This report presents studies of glucose transport in isolated rabbit enterocytes by using a fluorescent derivative of D-glucose. The dye allowed examining the relation between the toxic effect of OA and cellular mechanisms involved in glucose transport. The central findings are: (i) OA potentiates decrease on glucose uptake due to protein kinase A (PKA) inhibitors such as H89; and (ii) the increase of sugar uptake induced by the protein kinase C (PKC) inhibitor chelerythrine is enhanced by OA. Importance of this work is justified by the need to determine molecular targets of diarrheic toxins in intestinal cells.
Louzao
M C
MC
Departamento de Farmacología, Facultad de Veterinaria de Lugo, Universidad de Santiago de Compostela, Lugo, Spain.
Vieytes
M R
MR
Fontal
O
O
Botana
L M
LM
D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000378:metabolism; D003967:Diarrhea / Q000378:metabolism; D020895:Enterocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008387:Marine Toxins / Q000494:pharmacology; D019319:Okadaic Acid / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits
D004791:Enzyme Inhibitors; D008387:Marine Toxins; D019319:Okadaic Acid; D003847:Deoxyglucose; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D009327:4-Chloro-7-nitrobenzofurazan; D005947:Glucose; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose