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Effect of Carbachol and 56 mM‐Potassium Chloride on the Cyclic AMP‐Mediated Induction of Tyrosine Hydroxylase in Neuroblastoma Cells in Culture
Author(s) -
Tank A.W.,
Weiner N.
Publication year - 1981
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.1471-4159.1981.tb01623.x
Subject(s) - carbachol , endocrinology , medicine , adenylate kinase , cyclase , phosphodiesterase , activator (genetics) , chemistry , tyrosine hydroxylase , prostaglandin e , protein kinase a , biology , kinase , stimulation , enzyme , biochemistry , receptor , dopamine
Tyrosine hydroxylase (TH) activity is increased two‐ to threefold in neuroblastoma cell line NBP 2 maintained in culture for 48 h in the presence of either the inhibitor of cyclic AMP‐phosphodiesterase (PDE), 4‐(3‐butoxy‐4‐methoxybenzyl)‐2‐imidazolidinone (RO 20‐ 1724), or the activator of adenylate cyclase, prostaglandin E 1 (PGE 1 ). Cyclic AMP levels are elevated 70–80% and 30–40% throughout the 48‐h treatment with RO 20‐1724 and PGE 1 , respectively. Carbachol does not affect either basal TH activity or cyclic AMP levels in the cells. However, the cholinergic agonist delays the induction of TH elicited by either RO 20‐1724 or PGE 1 . This delay is prevented by atropine. The elevation in cyclic AMP levels elicited by either RO 20‐1724 or PGE 1 is blocked for 1 h or 15 min. respectively, after treatment with carbachol. Cyclic AMP levels then begin to rise until they reach those levels observed in the presence of RO 20‐1724 or PGE 1 alone by 12 h or 1 h of treatment, respectively. Time course studies demonstrate that this transient inhibition of the elevation of cyclic AMP is associated with a 48‐h delay in the induction of TH elicited by either RO 20‐1724 or PGE 1 . In contrast, the induction elicited by 8‐bromo cyclic AMP is unaffected by carbachol. A depolarizing concentration (56 mM) of KCl produces a 24‐h delay in the induction of TH elicited by RO 20‐1724, without affecting the concomitant elevation of cyclic AMP produced by the PDE inhibitor. Furthermore, 56 mM‐KCl inhibits the induction of TH elicited by 8‐bromo cyclic AMP. It thus appears that carbachol delays the induction of TH by transiently inhibiting the elevation of cyclic AMP, whereas potassium depolarization delays the induction of TH by inhibiting a process with a site of action that is distal to the elevation of cyclic AMP.