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Desensitization of adenylate cyclase and cyclic AMP flux during the early stages of liver regeneration
Author(s) -
Mahler Stephen M.,
Wilce Peter A.
Publication year - 1988
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041360111
Subject(s) - cyclase , adenylate kinase , glucagon , endocrinology , phosphodiesterase , medicine , biology , ibmx , growth hormone releasing hormone receptor , liver regeneration , intracellular , hormone , receptor , regeneration (biology) , microbiology and biotechnology , biochemistry , hormone receptor , stimulation , enzyme , forskolin , cancer , breast cancer
Liver regeneration is controlled by a complex network of interactions between hormones, growth factors, and a variety of hepatotrophic factors. Transient increases in cAMP in the early stages of liver regeneration that are necessary for DNA synthesis and subsequent mitosis have been reported; however, studies on the mechanisms that control cellular cAMP levels during liver regeneration, namely adenylate cyclase activity, cAMP‐dependent phosphodiesterase activity, and cAMP efflux from the cell, have been generally incomplete. In this study we have shown that although there are three peaks in intracellular cAMP levels in the first 24 hours after partial hepatectomy, the adenylate cyclase activity stimulated by glucagon, prostaglandin E 2 , adrenaline, and fluoride in vitro decreases with time. K d and B MAX of hepatocyte glucagon and β receptors were similar to the sham controls. Our results are consistent with a mixed homologous/heterologous desensitization of the adenylate cyclase system. There was also a loss of cAMP‐dependent phosphodiesterase activity after partial hepatectomy. We speculate that even though the hormone‐stimulated adenylate cyclase system has been desensitized, the system retains the ability to respond to the transient pulses of the variety of hormones secreted after partial hepatectomy and thus raise the intracellular concentration of cAMP. The decrease in cAMP‐dependent phosphodiesterase may be necessary to prevent rapid breakdown of cAMP.