Production, uptake, and metabolic effects of cyclic AMP in the bivascularly perfused rat liver. 1997

J Constantin, and F Suzuki-Kemmelmeier, and N S Yamamoto, and A Bracht
Laboratory of Liver Metabolism, University of Maringa, Brazil.

Production, uptake, and metabolic effects of cyclic AMP (cAMP) were measured in the bivascularly perfused rat liver in anterograde and retrograde perfusion. Glucagon, cAMP, N6,2'-O-dibutyryl cAMP and N6-monobutyryl cAMP were infused into the portal vein (anterograde perfusion), the hepatic vein (retrograde perfusion), or the hepatic artery (anterograde and retrograde perfusion) in order to reach different cell populations. The following results were obtained: (1) cAMP release caused by glucagon was directly proportional to the cell spaces that were accessible via the hepatic artery in anterograde and retrograde perfusion; since the metabolic effects of glucagon were not proportional to the accessible cell spaces, this observation also implies a disproportion between cAMP release and metabolic effects of the hormone; (2) when cAMP and N6,2'-O-dibutyryl cAMP were given to all liver cells (e.g. when infused into the portal vein), their metabolic effects were qualitatively and quantitatively the same and qualitatively equal to the effects of glucagon; (3) the changes caused by cAMP were a function of the cell spaces that can be reached via the hepatic artery in anterograde and retrograde perfusion; this behaviour contrasts markedly with that of glucagon, whose metabolic effects were practically independent of the accessible cell spaces; and (4) the effects of N6,2'-O-dibutyryl cAMP and N6-monobutyryl cAMP were independent of the cell spaces that were accessible via the hepatic artery in anterograde and retrograde perfusion; in this respect their behaviour was equal to that of glucagon. It is apparent that exogenously added cAMP mimicked the metabolic effects of glucagon in the liver only when it was supplied to all liver cells. Since glucagon, N6,2'-O-dibutyryl cAMP, and N6-monobutyryl cAMP were able to produce a full response even when given to only 30% of the liver parenchyma, it was concluded that cAMP production under the stimulus of glucagon or in consequence of the metabolic transformation of N6,2'-O-dibutyryl cAMP and N6-monobutyryl cAMP occurs in a compartment to which exogenous cAMP has no access. cAMP generated within this compartment is possibly able to diffuse from cell to cell.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008112 Liver Glycogen Glycogen stored in the liver. (Dorland, 28th ed) Hepatic Glycogen,Glycogen, Hepatic,Glycogen, Liver
D008297 Male Males
D010477 Perfusion Treatment process involving the injection of fluid into an organ or tissue. Perfusions
D003994 Bucladesine A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed) Dibutyryl Adenosine-3',5'-Monophosphate,Dibutyryl Cyclic AMP,(But)(2) cAMP,Bucladesine, Barium (1:1) Salt,Bucladesine, Disodium Salt,Bucladesine, Monosodium Salt,Bucladesine, Sodium Salt,DBcAMP,Dibutyryl Adenosine 3,5 Monophosphate,N',O'-Dibutyryl-cAMP,N(6),0(2')-Dibutyryl Cyclic AMP,AMP, Dibutyryl Cyclic,Adenosine-3',5'-Monophosphate, Dibutyryl,Cyclic AMP, Dibutyryl,Dibutyryl Adenosine 3',5' Monophosphate,Disodium Salt Bucladesine,Monosodium Salt Bucladesine,N',O' Dibutyryl cAMP,Sodium Salt Bucladesine
D005934 Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal GLUCAGON-LIKE PEPTIDES. Glucagon is secreted by PANCREATIC ALPHA CELLS and plays an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511) Glucagon (1-29),Glukagon,HG-Factor,Hyperglycemic-Glycogenolytic Factor,Proglucagon (33-61),HG Factor,Hyperglycemic Glycogenolytic Factor
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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