G. Forstner et al., MUCIN SECRETION BY T84 CELLS - STIMULATION BY PKC, CA-2-KINASE ACTIVATED BY CA-2+ IONOPHORE(, AND A PROTEIN), The American journal of physiology, 264(6), 1993, pp. 1096-1102
T84 adenocarcinoma cells were stimulated to secrete mucin by the phorb
ol ester phorbol 12-myristate 13-acetate (PMA) and Ca2+ ionophores A23
187 and ionomycin. In Ca2+-containing media, maximal stimulation by PM
A was significantly inhibited by staurosporine, but maximal A23187-sti
mulated secretion was not affected. Downregulation of protein kinase C
(PKC) reduced maximal PMA-stimulated secretion without affecting the
response to A23187. Thus PKC activation is not required for maximal Ca
2+-mediated mucin secretion. PMA stimulated secretion in low-Ca2+ medi
a, with and without intracellular chelation of Ca2+ by ,2-bis(2-aminop
henoxy)ethane-N,N,N',N'-tetraacetic acid. Surprisingly, Ca2+ ionophore
s also stimulated secretion under the same circumstances. Persistent A
23187-stimulated secretion was strongly inhibited by the protein kinas
e inhibitors staurosporine and H-7. Secretion in Ca2+-containing media
was also inhibited at submaximal levels of Ca2+-ionophore stimulation
. These results indicate that PKC and Ca2+ stimulate mucin exocytosis
independently. Ca2+ ionophores also stimulate secretion via a protein-
kinase dependent pathway. Enhancement of protein kinase inhibition at
lower Ca2+ concentrations suggests that the response could be mediated
by a Ca2+ ionophore-induced depletion of an intracellular Ca2+ pool.