Interaction between adrenaline and epidermal growth factor in the control of liver glycogenolysis in mouse.
Epidermal growth factor (EGF) stimulates glycogenolysis in mouse liver, but the effect requires concentrations that are only achieved in plasma upon adrenergic stimulation of EGF release from submandibular salivary glands. Thus, we studied the interaction between adrenaline and EGF in liver glycogen metabolism, both in whole animals and in isolated hepatocytes. Adrenaline administered to anesthetized mice stimulated both the endocrine secretion of EGF from submandibular salivary glands and the degradation of glycogen in the liver. In sialoadenalectomized mice, adrenaline administration did not increase plasma EGF concentration. In these animals, the glycogenolytic response to adrenaline was enhanced. The sensitivity of hepatocytes to adrenaline was similar in cells from sialoadenalectomized and sham-operated mice. EGF, added to isolated hepatocytes, reduced the glycogenolytic effect of adrenaline (the maximal effect but not the ED50). Adrenaline stimulated glycogen degradation through both an alpha1-adrenergic mediated Ca2+ increase and a beta-adrenergic-mediated cAMP increase. EGF did not interfere with the rise of cytosolic Ca2+ but decreased the cAMP signal. EGF did not decrease the glycogenolytic effect of phenylephrine or VP (which increased cytosolic Ca2+ but not cAMP), but EGF decreased both the glycogenolytic effect and the cAMP signal generated by glucagon or forskolin. EGF did not interfere with the glycogenolytic effect of CPT-cAMP or bt2-cAMP. The effect of EGF on cAMP was blocked by 3-isobutyl-1-methylxanthine. These results demonstrate that the effect of EGF on the glycogenolytic action of adrenaline involves interference with the generation of the cAMP signal. We suggest that EGF induces such an effect through the activation of a phosphodiesterase.
Grau
M
M
Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Spain.
Soley
M
M
Ramírez
I
I
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000097:blood / Q000494:pharmacology* / Q000502:physiology*; D004837:Epinephrine / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D051379:Mice; D010656:Phenylephrine / Q000494:pharmacology; D010762:Phosphorylase a / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013363:Submandibular Gland / Q000502:physiology* / Q000601:surgery
D008112:Liver Glycogen; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D004815:Epidermal Growth Factor; D000242:Cyclic AMP; D010762:Phosphorylase a; D007545:Isoproterenol; D002118:Calcium; D004837:Epinephrine