Guanylyl cyclase C is up-regulated by nonparenchymal cells and hepatocytes in regenerating rat liver.
Guanylyl cyclase C (GC-C) is the receptor for the heat-stable enterotoxin produced by bacteria as well as for the newly discovered mammalian hormones guanylin and uroguanylin. Ligand activation of GC-C causes it to produce cyclic GMP inside target cells. Although once thought to be restricted to the intestine, GC-C mRNA has recently been detected in other tissues. We now examine the expression, localization, and activation of this glycoprotein after partial hepatectomy in rats. By immunoblot analysis, GC-C protein appeared as early as 4 h after partial hepatectomy, reached its maximal expression (a 30-fold increase) between 24 and 48 h, and returned to low baseline levels at 96 h. During the regenerative period, we detected two GC-C isoforms that differed in their size, temporal expression, and carbohydrase sensitivities. We showed that 131- and 140-kDa GC-C isoforms represented immature and mature GC-C glycoforms on the basis of endoglycosidase H and PNGase sensitivities. Cell separation experiments revealed that the nonparenchymal cell fractions of regenerating liver contained four times as much GC-C as purified hepatocytes. Immunohistochemistry confirmed these findings. The exuberant expression of GC-C by nonparenchymal cells and, to a lesser extent, hepatocytes suggests a role for cyclic GMP in liver regeneration.
Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2576, USA.
L A
LA
Scheving
W E
WE
Russell
D000818:Animals; D066246:ErbB Receptors / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism*; D006498:Hepatectomy; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
D012333:RNA, Messenger; D018000:Receptors, Peptide; D066246:ErbB Receptors; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled