Mannose 6-phosphate potentiates insulin-like growth factor II-stimulated inositol trisphosphate production in proximal tubular basolateral membranes.
To ascertain whether mannose 6-phosphate affects insulin-like growth factor (IGF) II stimulation of phospholipase C activity in the basolateral membrane of the renal proximal tubular cell, we determined the effect of mannose 6-phosphate on IGF II-stimulated production of inositol trisphosphate (Ins-P3) in isolated basolateral membranes. Production of Ins-P3 measured in the presence of 10(-10), 10(-9), or 10(-8) M rat IGF II was potentiated approximately 2-fold by inclusion of 5 mM mannose 6-phosphate in incubations. Mannose 6-phosphate had no effect on Ins-P3 production in the absence of IGF II. Neither mannose 1-phosphate, mannose, glucose 6-phosphate, nor fructose 1-phosphate exerted similar potentiation. Enhancement of IGF II-stimulated Ins-P3 production required concentrations on the order of several millimolar mannose 6-phosphate. Total and specific binding of 10(-10) M 125I-IGF II to basolateral membranes was significantly increased by 5 mM mannose 6-phosphate. However, there was no significant effect on total or specific binding of 10(-9) or 10(-8) M 125I-IGF II. Our findings suggest that mannose 6-phosphate potentiates stimulation of phospholipase C by IGF II in the basolateral membrane of the renal proximal tubular cell and that potentiation is mediated via a mechanism in addition to enhanced binding of IGF II. Such potentiation could reflect a role for the mannose 6-phosphate moiety as a modulator of IGF II "signal" transmission in vivo.
Rogers
S A
SA
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Hammerman
M R
MR
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004591:Electrophoresis, Polyacrylamide Gel; D006600:Hexosephosphates / Q000494:pharmacology*; D006601:Hexoses / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008360:Mannosephosphates / Q000494:pharmacology*; D011994:Recombinant Proteins; D013002:Somatomedins / Q000494:pharmacology*; D013403:Sugar Phosphates / Q000378:metabolism*
D006600:Hexosephosphates; D006601:Hexoses; D007295:Inositol Phosphates; D008360:Mannosephosphates; D011994:Recombinant Proteins; D013002:Somatomedins; D013403:Sugar Phosphates; C027693:mannose-6-phosphate; D007335:Insulin-Like Growth Factor II; D015544:Inositol 1,4,5-Trisphosphate