title: Kinetics of inositol 1,4,5-trisphosphate and inositol cyclic 1:2,4,5-trisphosphate metabolism in intact rat parotid acinar cells. Relationship to calcium signalling.
abstract: Stimulation of rat parotid acinar cells by the muscarinic cholinergic receptor agonist methacholine results in the formation of inositol 1,4,5-trisphosphate [1,4,5)IP3) and inositol cyclic 1:2,4,5-trisphosphate [c1:2,4,5)IP3) which, after 40 min, accumulate to a ratio of 1:0.57. The turnover rates of these inositol trisphosphates have been determined in cholinergically stimulated rat parotid cells by measuring the degradation of the 3H-labeled compounds following receptor blockade. (1,4,5)IP3 is rapidly metabolized, with a half-time of 7.6 s; (c1:2,4,5)IP3 declines much more slowly with a half-time of almost 10 min. Because the formation and metabolism of (c1:2,4,5)IP3 are so slow, (c1:2,4,5)IP3 gradually accumulates upon prolonged receptor activation. Inositol trisphosphate turnover was compared to the receptor-mediated changes in cytoplasmic Ca2+ concentration, as measured by the fluorescent Ca2+ indicator, fura-2. The Ca2+ signal decays upon termination of inositol phosphate formation and returns to base line within 30 s. Thus, while (c1:2,4,5)IP3 may have some yet unknown biological effects on Ca2+ homeostasis, its metabolism seems far too slow to be the primary regulator of cytosolic Ca2+ levels under long term stimulatory conditions. The rate at which the Ca2+ signal decays is, however, somewhat slowed after prolonged agonist stimulation. Furthermore, the capacity of the cells to mobilize intracellular Ca2+ in response to a second agonist stimulation is slightly delayed when the duration of the first stimulus is prolonged. The results suggest that the regulation of cytoplasmic Ca2+ levels may be more complicated than initially realized and could depend on the combined actions of more than one inositol polyphosphate.
authors: Calcium Regulation Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
authors: A R
authors: AR
authors: Hughes
authors: H
authors: H
authors: Takemura
authors: J W
authors: JW
authors: Putney
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013373:Substance P / Q000494:pharmacology; D013403:Sugar Phosphates / Q000378:metabolism*
chemical_list: D007295:Inositol Phosphates; D013403:Sugar Phosphates; D013373:Substance P; D015544:Inositol 1,4,5-Trisphosphate; C049924:inositol-1,2-cyclic-4,5-triphosphate; D002118:Calcium