title: Stimulus-responsive and rapid formation of inositol pentakisphosphate in cultured adrenal chromaffin cells.
abstract: When [3H]inositol-prelabeled cultured bovine adrenal chromaffin cells were stimulated with high K+ (56 mM) and nicotine (10 microM), a large and transient increase in [3H]inositol 1,3,4,5,6-pentakisphosphate (InsP5) accumulation was observed. The accumulation reached the maximum level at 15 s and then declined to the basal level at 2 min. The time course of accumulation of InsP5 was parallel to that of [3H]inositol 1,4,5-trisphosphate (Ins(1,4,5)P3). Angiotensin II (Ang II) (10 microM) rapidly accumulated InsP5, but the level was sustained for 2 min. With a slower time course and a lesser amount than InsP5, high K+, nicotine, and Ang II caused an accumulation of [3H]inositol 1,3,4,5-tetrakisphosphate and [3H]inositol hexakisphosphate. Veratridine (100 microM), maitotoxin (10 ng/ml), ATP (30 microM), platelet-derived growth factor (10 ng/ml), and endothelin (10 ng/ml) also induced the InsP5 accumulation. High K+, nicotine, veratridine, and maitotoxin induced an increase in 45Ca2+ uptake, whereas Ang II, ATP, platelet-derived growth factor, and endothelin did not cause 45Ca2+ uptake. Nifedipine, a calcium channel antagonist, inhibited the high K(+)-induced InsP5 accumulation but failed to affect the Ang II-induced InsP5 accumulation. In an EGTA-containing and Ca2(+)-depleted medium, the high K(+)-induced InsP5 accumulation was completely inhibited, whereas the InsP5 accumulation induced by Ang II was not significantly inhibited. 12-O-tetradecanoylphorbol-13-acetate inhibited partially the Ang II-induced InsP5 accumulation but failed to inhibit the high K(+)-induced accumulation. In those experiments, the changes of InsP5 accumulation were closely correlated to those of Ins(1,4,5)P3. In the chromaffin cell homogenate, [3H] Ins(1,4,5)P3 was converted eventually to [3H]InsP5 through [3H]inositol 1,3,4,6-tetrakisphosphate. Taken together, the above results suggest that InsP5 is rapidly formed by a variety of stimulants and that the formation of InsP5 may occur through two mechanisms, i.e. Ca2+ uptake-dependent and Ca2+ uptake-independent ones in cultured adrenal chromaffin cells.
authors.affiliation: Department of Pharmacology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sasakawa
authors.forename: T
authors.initials: T
authors.lastname: Nakaki
authors.forename: R
authors.initials: R
authors.lastname: Kato
mesh_terms: D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004533:Egtazic Acid / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000096:biosynthesis* / Q000302:isolation & purification; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D008387:Marine Toxins / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D035964:Oxocins; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D000095702:Polyether Toxins
chemical_list: D002118:Calcium; D004533:Egtazic Acid; D016232:Endothelins; D007294:Inositol; D007295:Inositol Phosphates; D008094:Lithium; D008387:Marine Toxins; D009538:Nicotine; D009543:Nifedipine; D035964:Oxocins; D010982:Platelet-Derived Growth Factor; D011188:Potassium; D013755:Tetradecanoylphorbol Acetate; D014701:Veratridine; C013571:inositol pentaphosphate; C020394:maitotoxin; D000095702:Polyether Toxins