Cyclosporin A antagonizes phenylephrine, oxytocin and angiotensin effects on glucose metabolism in rat thymus lymphocytes.
Effects of phenylephrine, oxytocin and angiotensin on fructose 2,6-bisphosphate (Fru 2,6-P2) content and glycolytic parameters were studied in incubated thymus lymphocytes. These hormones modified Fru 2,6-P2 content dependent upon the energetic status of the cells. In non-preincubated thymus lymphocytes (with relatively high levels of glycogen and ATP), phenylephrine, oxytocin and angiotensin depressed Fru 2,6-P2 content in a dose-dependent manner. The opposite was found when the cells were preincubated for 2 h without substrates (low levels of ATP and glycogen). Changes in lactate release were less evident, but significant. Phenylephrine did not modify the maximal activities of phosphofructokinase (PFK)-1 or PFK-2. However, both submaximal PFK-1 and PFK-2 activities were inhibited by phenylephrine, and the response to exogenous Fru 2,6-P2 on PFK-1 was also altered. The activities of Fru 1,6-P2 and pyruvate kinase were not modified by phenylephrine or A23187 treatment. Simultaneous presence of Cyclosporin A (CsA), an immunosuppressive drug, antagonizes the alpha-adrenergic effect on Fru 2,6-P2 content. CsA alone did not alter basal levels of ATP, hexose phosphate or Fru 2,6-P2, and its opposing effect to alpha-agonist was dose-dependent. CsA cannot change the positive action of PMA or the negative action of A23187 on Fru 2,6-P2 content. The present data suggest that CsA acts prior to calcium liberation and protein kinase C activation. Different possible molecular models are discussed.
Gualberto
A
A
Dept. de Bioquímica Médica y Biología Molecular, Facultad de Medicina, Universidad de Sevilla, Spain.
Conde
M
M
Sobrino
F
F
D000255:Adenosine Triphosphate / Q000378:metabolism; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005635:Fructosediphosphates / Q000032:analysis; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010121:Oxytocin / Q000037:antagonists & inhibitors*; D010656:Phenylephrine / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology
D005635:Fructosediphosphates; D007773:Lactates; D000804:Angiotensin II; D010656:Phenylephrine; D019344:Lactic Acid; D000001:Calcimycin; D010121:Oxytocin; C027652:fructose 2,6-diphosphate; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate