Effect of albumin on adenylate cyclase receptor-related signal transduction of human peripheral blood mononuclear cells.
In the present study we investigated in vitro the effect of human serum albumin (HSA) on receptor-stimulated cAMP production in isolated human peripheral blood mononuclear cells (PBMC). The cAMP production is strongly correlated with the pH of the medium during long incubations with albumin. Adenylate cyclase is stimulated by receptor agonists like histamine, forskolin, prostaglandin E2 and the beta-adrenergic agonist isoprenaline, in the presence or absence of HSA. This protein, at concentrations above 0.1%, dose-dependently inhibits both basal and agonist-stimulated cAMP levels in PBMC. In the presence of 0.5% HSA a significant reduction of 30-60% (cell batch dependent) is induced, a reduction which is not incubation time dependent. Washing the cells after a period of incubation with 2% HSA does not reverse the HSA-induced cAMP inhibition. Oleic acid-evoked conformational changes in HSA were not capable of influencing the inhibition processes of HSA on the isoprenaline-stimulated cAMP production. Structure-controlled interactions between HSA and membrane or adenylate cyclase are therefore unlikely. Bovine serum albumin and chicken albumin had different effects upon the agonist-stimulated cAMP production as compared with HSA. At this moment no explanation for this behavior can be provided. The findings indicate that albumin may inhibit non-specifically cAMP production in PBMC and possibly influences membrane-controlled processes.
Fischer
M J
MJ
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Utrecht University, The Netherlands.
van Oosterhout
A J
AJ
Janssen
L H
LH
Nijkamp
F P
FP
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D004789:Enzyme Activation; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007545:Isoproterenol / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D012709:Serum Albumin / Q000494:pharmacology*; D015398:Signal Transduction
D012709:Serum Albumin; D005576:Colforsin; D006632:Histamine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine