Mechanism of action of GTP in the induction of Ca2+ release from hepatic microsomes.

Abstract:

:The mechanism by which GTP induces Ca2+ release from Ca2(+)-preloaded rat hepatic microsomes was studied. In the same concentration range as that for Ca2+ release, GTP inhibited the initial rate of ATP-driven Ca2+ uptake. It also inhibited the formation by ATP of the phosphorylated intermediate of Ca2(+)-ATPase, which had previously been identified by us as a 97-116 kDa protein (Fleschner, C.R., et al. (1985) Biochem. J. 226, 839). Vanadate, an inhibitor of Ca2(+)-ATPase, also caused Ca2+ release in a similar fashion, but its effect was not additive to that of GTP. Although the non-metabolizable GTP analogues, GMPPNP and GTP gamma S, did not cause Ca2+ release by themselves, GTP gamma S completely and GMPPNP partially blocked the effect of GTP. Pretreatment of vesicles with either cholera or pertussis toxin did not alter the responsiveness to GTP. These results indicate that GTP inhibits microsomal Ca2(+)-ATPase, independently of the Gs and Gi proteins. Because a decrease in Ca2+ uptake results in a net increase in Ca+ release, this effect of GTP seems to account, at least partially, for the GTP-induced Ca2+ release from microsomes.

journal_name

J Biochem

journal_title

Journal of biochemistry

authors

Kimura S,Higham S,Robison BC,Kraus-Friedmann N

doi

10.1093/oxfordjournals.jbchem.a123084

subject

Has Abstract

pub_date

1990-04-01 00:00:00

pages

550-3

issue

4

eissn

0021-924X

issn

1756-2651

journal_volume

107

pub_type

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