Involvement of cyclic adenosine monophosphate-dependent protein kinase isozymes in tissue plasminogen activator secretion by rat Sertoli cells stimulated with follicle-stimulating hormone in vitro.
This study was undertaken to investigate, in freshly isolated rat Sertoli cells, the physiological function of the type I and type II cyclic adenosine monophosphate (cAMP)-dependent protein kinase isozymes in tissue-type plasminogen activator secretion and the regulation of this cAMP process by follicle-stimulating hormone (FSH). Follicle-stimulating hormone-induced tissue-type plasminogen activator secretion depends upon intracellular cAMP levels. The changes in cAMP amounts required to activate maximally the tissue-type plasminogen activator secretion are extremely small, a cAMP threshold having to be reached for triggering the tissue-type plasminogen activator output. Intact Sertoli cells were incubated with combinations of cAMP analogs specific for each cAMP-dependent protein kinase type and complementary in their cAMP binding site on the cAMP-dependent protein kinase regulatory subunits: 8-aminohexylamino-cAMP = type 1, site 1; 8-thiomethyl-cAMP = type II, site 1 and N6-benzoyl-cAMP = types I/II, site 2. This allowed us to activate selectively each cAMP-dependent protein kinase type in a synergistic manner and then to evaluate their respective influence in the specific tissue-type plasminogen activator response. We establish that both of the cAMP-dependent protein kinase types are present and functional; the activity of the type I isozyme is preponderant (60%) in the cAMP-dependent tissue-type plasminogen activator secretion. Likewise, when these cAMP analogs were coupled with endogenously generated cAMP by FSH or forskolin, both of the cAMP-dependent protein kinase types were involved in the tissue-type plasminogen activator production.(ABSTRACT TRUNCATED AT 250 WORDS)
Laurent-Cadoret
V
V
Station de Physiologie de la Reproduction des Mammifères Domestiques (PRMD), INRA/CNRS, URA, Nouzilly, France.
Guillou
F
F
Combarnous
Y
Y
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D007527:Isoenzymes / Q000502:physiology*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000502:physiology*; D051381:Rats; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism*; D013873:Thionucleotides; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D013873:Thionucleotides; D005576:Colforsin; C050086:N(6)-benzoyl-cyclic AMP; C067297:8-aminohexylamino cAMP; C011306:8-(methylthio)cyclic 3',5'-adenosine monophosphate; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D011494:Protein Kinases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D010959:Tissue Plasminogen Activator; D015056:1-Methyl-3-isobutylxanthine