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Depolarization and Agonist‐Stimulated Changes in Inositol 1,4,5‐Trisphosphate and Inositol 1,3,4,5‐Tetrakisphosphate Mass Accumulation in Rat Cerebral Cortex
Author(s) -
Challiss R. A. John,
Nahorski Stefan R.
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb08255.x
Subject(s) - depolarization , inositol phosphate , endocrinology , inositol , medicine , carbachol , chemistry , muscarinic acetylcholine receptor , stimulation , physostigmine , second messenger system , acetylcholine , agonist , receptor , biology , biochemistry
Muscarinic receptor stimulation or depolarization with elevated extracellular K + induced rapid and sustained increases in mass accumulations of myo ‐inositol 1,4,5‐trisphosphate [Ins(1,4,5)P 3 ] and myo ‐inositol 1,3,4,5‐tetrakis‐phosphate [Ins(1,3,4,5)P 4 ] in cerebral cortex slices. Synergistic but transient responses of both inositol polyphosphate second messengers were observed when slices were stimulated with carbachol under depolarizing conditions; this synergy was observed as an increase in the maximal responsiveness, with no significant change in EC 50 values forcarbachol. Omission of buffer Ca 2+ ([Ca 2+ ] e 10–20 μ M ) reduced basal lns (1,4,5)P 3 and Ins(1,3,4,5)P 4 concentrations; the relative stimulatory effects of muscarinic receptor stimulation were maintained, but the effects of depolarization were markedly attenuated under these conditions. A component of the response to depolarization appeared to be indirectly mediated by the release of acetylcholine, because the K + ‐evoked increase in Ins(1,3,4,5)P 4 was enhanced by the cholinesterase inhibitor physostigmine, and was partially attenuated by atropine. An additive suppression by nitrendipine suggests that entry of Ca 2+ through L‐type Ca 2+ channels may serve to accelerate phosphorylation of Ins(1,4,5)P 3 by 3‐kinase. Norepinephrine did not significantly increase Ins(1,4,5)P 3 or Ins(1,3,4,5)P 4 accumulation; however, in the presence of depolarizing K + , norepinephrine caused a dramatic increase in Ins(1,3,4,5)P 4 mass accumulation. In contrast, the excitatory amino acid quisqualate caused significant increases in the mass accumulations of both inositol polyphosphates measured, with no further increase being observed under depolarizing conditions. The results are discussed with respect to the interactive effects of agonist and depolarization stimuli on inositol polyphosphate accumulation which might more accurately reflect the conditions pertaining in vivo.