Effects of adrenergic agonists and antagonists on autophagic activity in isolated rat liver cells.
The effect of various adrenergic agonists on autophagic sequestration--measured as the transfer of electroinjected [3H]raffinose from cytosol to vacuoles of the autophagic pathway--was investigated. Epinephrine and other agonists with alpha-effects inhibited sequestration through a specific alpha 1-adrenergic, i.e. prazosin-sensitive, mechanism. The beta-adrenergic agonist isoproterenol also inhibited sequestration, but by a non-beta-specific (propranolol-insensitive) mechanism. All sequestration-inhibitory agents suppressed overall autophagic-lysosomal proteolysis. The inhibitory action of the adrenergic agonists on protein metabolism was not specific to the autophagic pathway since protein synthesis was suppressed as well. However, intracellular levels of ATP were not adversely affected, ruling out the possibility that the agonists might be generally cytotoxic.
Gordon
P B
PB
Department of Tissue Culture, Norwegian Radium Hospital, Montebello, Oslo.
Holen
I
I
Seglen
P O
PO
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D011506:Proteins / Q000378:metabolism; D011887:Raffinose / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D013565:Sympatholytics / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology*; D014617:Vacuoles / Q000378:metabolism
D011506:Proteins; D013565:Sympatholytics; D013566:Sympathomimetics; D000255:Adenosine Triphosphate; D011887:Raffinose