Ligand binding and internalization by the rat hepatic asialoglycoprotein receptor does not generate polyphosphoinositide derived second messengers.
Recent studies suggest that protein kinase C and, thus, possibly the rate of inositol phospholipid hydrolysis may regulate the function and distribution of the asialoglycoprotein (or galactosyl) receptor on isolated rat hepatocytes (Takahashi et al., Biochem. Biophys. Res. Commun., 1985, 126, 1054; Fallon and Schwartz, J. Biol. Chem., 1986, 261, 15081). We have studied the effects of asialoorosomucoid (ASOR) on the hydrolysis of [32P]-inositol phospholipids in isolated rat hepatocytes. When internalization of ASOR is maximal at 310 molecules/cell/sec, there is neither a decrease in the amount of [32P]-phosphatidylinositol-4,5-bisphosphate (PIP2) nor an increase in [32P]-phosphatidic acid (PA) up to 30 min after stimulation. On the other hand, 10(-6)M vasopressin, which was used as a positive control, caused a 35-40% decrease in the level of [32P]-PIP2 and a 70-80% increase in [32P]-PA within 30 sec. Addition of orosomucoid or ASOR, even at concentrations 1000-times the Kd, did not change the levels of any of the six phospholipids tested. Similarly, addition of ASOR did not increase the levels of soluble [3H]-inositol phosphates, whereas vasopressin caused a 6-fold increase in [3H]-inositol-1,4-diphosphate (IP2) and a 4-fold increase in [3H]-inositol-1,4,5-triphosphate (IP3) in isolated rat hepatocytes prelabeled with [3H]-inositol. We conclude that the receptor mediated endocytosis of asialoglycoproteins by rat hepatocytes does not stimulate hydrolysis of the inositol phospholipids.
Medh
J D
JD
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550.
Haynes
P A
PA
Weigel
P H
PH
LaBelle
E F
EF
D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D006868:Hydrolysis; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D008024:Ligands; D008297:Male; D009961:Orosomucoid / Q000031:analogs & derivatives / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000378:metabolism*; D015290:Second Messenger Systems; D014667:Vasopressins / Q000494:pharmacology
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D007295:Inositol Phosphates; D008024:Ligands; D009961:Orosomucoid; D010716:Phosphatidylinositols; D010743:Phospholipids; D011971:Receptors, Immunologic; C017030:asialoorosomucoid; D014667:Vasopressins