Regulation of secretion in cultured tracheal serous cells by protein kinases A and C.
We recently reported that cultured gland serous cells release chondroitin sulfate proteoglycans (CSPGs) in response to beta-adrenergic agonists. In this study, we analyzed this regulatory pathway and other cellular mechanisms responsible for CSPG secretion. We show the following. 1) Isoproterenol increased CSPG secretion in a concentration-dependent manner, with maximal stimulation (50%) obtained at 10(-5) M; at this concentration, the beta-agonist also stimulated protein kinase A (PKA) by 50%, whereas it increased cellular adenosine 3',5'-cyclic monophosphate (cAMP) content by 300%. 2) Phenylephrine (10(-5) M), 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (1.6 x 10(-7) M), and A23187 (10(-6) M) also stimulated CSPG secretion; this stimulation was concomitant with protein kinase C (PKC) translocation from cytosol to membrane, was blocked by sphingosine (2 x 10(-5) M), and was additive with that elicited by isoproterenol. 3) All PKC activators potentiated the isoproterenol-induced increased in cAMP accumulation without modifying the activation of PKA elicited by the beta-agonist. Our results indicate that although the signaling pathways triggered by alpha- and beta-adrenergic agonists converge at the level of adenylate cyclase in tracheal serous cells, PKA and PKC independently regulate CSPG secretion.
Paul
A
A
Institut National de la Santé et de la Recherche Médicale U 181, Laboratoire de Biochimie, Faculté de Médecine-Saint-Antoine, Paris, France.
Mergey
M
M
Veissière
D
D
Hermelin
B
B
Cherqui
G
G
Picard
J
J
Basbaum
C B
CB
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology*; D012704:Serous Membrane / Q000166:cytology / Q000378:metabolism*; D013110:Sphingosine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014132:Trachea / Q000166:cytology / Q000378:metabolism*
D011508:Chondroitin Sulfate Proteoglycans; D000001:Calcimycin; D000242:Cyclic AMP; D011494:Protein Kinases; D011493:Protein Kinase C; D007545:Isoproterenol; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate