Inositol-phosphoglycan inhibits calcium oscillations in hepatocytes by reducing calcium entry.
Inositol-phosphoglycan (IPG) is a putative mediator of insulin action that has been shown to affect numerous biochemical processes. IPG, prepared from liver membranes, promptly inhibited phenylephrine- or vasopressin-induced [Ca2+]i oscillations when perfused over Fura-2-dextran injected rat hepatocytes. An antibody to IPG suppressed the inhibitory effect of insulin on the [Ca2+]i oscillations. Measurement of the rate of quench of cytoplasmic Fura-2 by extracellular Mn2+ showed that Ca2+ entry occurred continuously in the unstimulated cell and was not affected by phenylephrine or vasopressin. IPG, specifically, almost completely abolished the Mn2+ quench rate. Elevated extracellular [Ca2+] reversed the inhibitory effect of IPG on [Ca2+]i oscillations. We conclude that IPG inhibits the hepatocyte Ca2+ oscillatory by reducing the continuous Ca2+ influx that is required to sustain oscillations in [Ca2+]i.
Sanchez-Bueno
A
A
Department of Human Anatomy and Cell Biology, University of Liverpool, UK. antonio@liverpool.ac.uk
Greenwood
M R
MR
Varela-Nieto
I
I
Marrero
I
I
Gil
B
B
Mato
J M
JM
Cobbold
P H
PH
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D007295:Inositol Phosphates / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007329:Insulin Antagonists / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008345:Manganese / Q000378:metabolism; D017895:Manganese Compounds / Q000494:pharmacology; D008845:Microinjections; D009608:Nitrous Acid / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014667:Vasopressins / Q000494:pharmacology
D002712:Chlorides; D005456:Fluorescent Dyes; D007295:Inositol Phosphates; D007328:Insulin; D007329:Insulin Antagonists; D017895:Manganese Compounds; D011134:Polysaccharides; C028039:inositol phosphate glycan; D014667:Vasopressins; D010656:Phenylephrine; D008345:Manganese; C025340:manganese chloride; D002118:Calcium; D009608:Nitrous Acid; D016257:Fura-2