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PMID: 8172600 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A slowly ADP-ribosylated pertussis-toxin-sensitive GTP-binding regulatory protein is required for vasopressin-stimulated Ca2+ inflow in hepatocytes.

The Biochemical journal ·Vol. 299 ( Pt 2) ·1994-04-15 ·Pages 399-407

Berven LA, Hughes BP, Barritt GJ

Abstract

The roles of heterotrimeric GTP-binding regulatory proteins (G-proteins) and inositol polyphosphates in the mechanism by which vasopressin stimulates Ca2+ inflow in hepatocytes were investigated by using single cells loaded with fura2 by microinjection. Vasopressin-stimulated Ca2+ inflow was mimicked by microinjection of guanosine 5'-[gamma-thio]triphosphate (GTP[S]) or guanosine 5'-[beta gamma-imido]triphosphate to the cells, but not adenosine 5'-[gamma-thio]triphosphate (ATP[S]) or guanosine 5'-[beta-thio]diphosphate (GDP[S]). Extracellular Gd3+ (5 microM) inhibited both vasopressin- and GTP[S]-stimulated Ca2+ inflow. GDP[S], but not GMP, administered to hepatocytes by microinjection, completely inhibited vasopressin-stimulated Ca2+ inflow and partially inhibited vasopressin-induced release of Ca2+ from intracellular stores. The microinjection of pertussis toxin had no effect either on the release of Ca2+ from intracellular stores or on Ca2+ inflow induced by vasopressin, but completely inhibited changes in these processes induced by epidermal growth factor (EGF). Hepatocytes isolated from rats treated with pertussis toxin for 24 h exhibited no vasopressin- or GTP[S]-stimulated Ca2+ inflow, whereas the vasopressin-stimulated release of Ca2+ from intracellular stores was similar to that observed for control cells. Heparin or ATP[S] inhibited, or delayed the onset of, both vasopressin-induced release of Ca2+ from intracellular stores and vasopressin-stimulated Ca2+ inflow. Vasopressin-induced oscillations in intracellular [Ca2+] were observed in some heparin-treated cells. It is concluded that the stimulation by vasopressin of Ca2+ inflow to hepatocytes requires inositol 1,4,5-trisphosphate (InsP3) and, by implication, the pertussis-toxin-insensitive G-protein required for the activation of phospholipase C beta [Taylor, Chae, Rhee and Exton (1991) Nature (London) 350, 516-518], and another G-protein which is slowly ADP-ribosylated by pertussis toxin and acts between InsP3 and the putative plasma-membrane Ca2+ channel. EGF-stimulated Ca2+ inflow involves at least one G-protein which is rapidly ADP-ribosylated and is most likely required for InsP3 formation.

MeSH Terms
Adenosine Diphosphate Ribose/metabolism Adenosine Triphosphate/analogs & derivatives,pharmacology Animals Calcium/metabolism Cells, Cultured Epidermal Growth Factor/pharmacology Fluorescent Dyes GTP-Binding Proteins/metabolism Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology Guanosine Diphosphate/analogs & derivatives,pharmacology Heparin/pharmacology Kinetics Liver/drug effects,metabolism Male Pertussis Toxin Rats Rats, Wistar Thionucleotides/pharmacology Time Factors Vasopressins/pharmacology Virulence Factors, Bordetella/pharmacology
Chemicals
Fluorescent Dyes Thionucleotides Virulence Factors, Bordetella Vasopressins Guanosine Diphosphate Adenosine Diphosphate Ribose adenosine 5'-O-(3-thiotriphosphate) Guanosine 5'-O-(3-Thiotriphosphate) Epidermal Growth Factor guanosine 5'-O-(2-thiodiphosphate) Adenosine Triphosphate Heparin Pertussis Toxin GTP-Binding Proteins Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Berven L A
Department of Medical Biochemistry, School of Medicine, Flinders University, Adelaide, Australia.
Hughes B P
Barritt G J
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2990399
Published
1994-04-15
Pages
399-407
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1138286
Subset
IM
External Links
PubMed source DOI: 10.1042/bj2990399 PMC Full Text View journal details
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