AJP - Lung Cellular and Molecular Physiology, Vol 261, Issue 2 172-L177, Copyright © 1991 by American Physiological Society
Regulation of secretion in cultured tracheal serous cells by protein kinases A and C
A. Paul, M. Mergey, D. Veissiere, B. Hermelin, G. Cherqui, J. Picard and C. B. Basbaum
Institut National de la Sante et de la Recherche Medicale U 181, Laboratoire de Biochimie, Faculte de Medecine-Saint-Antoine, Paris, France.
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.
