Alpha 1-adrenergic inositol trisphosphate production in brown adipocytes is Na+ dependent.
In order to investigate the ionic requirements for inositol trisphosphate production, brown adipocytes were prelabelled with myo-[3H]inositol and the formation of inositol trisphosphates and inositol bisphosphates as a consequence of alpha 1-adrenergic stimulation was monitored. Omission of Ca2+ from the incubation medium diminished the norepinephrine-induced increase in inositol trisphosphate levels, but it would seem that this reduction can be fully accounted for by a decreased level of the 'inactive' isomer inositol 1,3,4-trisphosphate. Omission of Na+ fully abolished the norepinephrine-induced inositol trisphosphate response. However, it was observed that the presence of Li+ in the incubation medium could fully reconstitute the ability of the cells to yield the early response of inositol trisphosphate production; Li+ could, however, not substitute for Na+ in the entire alpha 1-adrenergic cellular pathway. It was concluded that the Na+-dependent step is found in the coupling mechanism between the alpha 1-receptor and the activation of the phosphodiesterase responsible for inositol trisphosphate production. Thus, all events in the alpha 1-adrenergic pathway which are consequences of IP3 production should appear to be Na+-dependent in these cells.
Nånberg
E
E
Wenner-Gren Institute, University of Stockholm, Sweden.
Nedergaard
J
J
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D004533:Egtazic Acid / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D008647:Mesocricetus; D009638:Norepinephrine / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012964:Sodium / Q000494:pharmacology*; D013403:Sugar Phosphates / Q000096:biosynthesis*
D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; D013403:Sugar Phosphates; D007294:Inositol; D004533:Egtazic Acid; D015544:Inositol 1,4,5-Trisphosphate; D008094:Lithium; D012964:Sodium; D009638:Norepinephrine