Paradoxical effects of retinal in neutrophil stimulation.
Retinal stimulates the activity of phospholipase C and superoxide (O2-) release in neutrophils. The latter response is comparable in magnitude to that observed when phorbol 12-myristate 13-acetate (PMA) is the stimulating agent. Cells treated with retinal, however, do not undergo degranulation, nor do they exhibit the formation of intracellular vesicles, as is commonly observed with other agents (e.g. Lochner, J. E., Badwey, J. A., Horn, W., and Karnovsky, M. L. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 7673-7677). Retinal promotes redistribution of the activity of protein kinase C from a soluble to a particulate fraction in neutrophils, and this redistribution precedes O2- release. Superoxide release stimulated with retinal, however, is largely insensitive to inhibitors of protein kinase C (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7); staurosporine). These compounds substantially block both O2- release and the phosphorylation of two proteins with molecular masses of about 47 and 49 kDa when the stimulus is PMA. The data indicate that retinal and PMA elicit the formation of active protein kinase C complexes of different natures, or that the mechanism of stimulation of O2- release by retinal does not involve this kinase. The significance of these observations to the common use of retinoids as inhibitors of protein kinase C is discussed.
Badwey
J A
JA
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
Horn
W
W
Heyworth
P G
PG
Robinson
J M
JM
Karnovsky
M L
ML
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002458:Cell Fractionation; D002462:Cell Membrane / Q000201:enzymology; D004533:Egtazic Acid / Q000494:pharmacology; D006168:Guinea Pigs; D007546:Isoquinolines / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000009:adverse effects / Q000378:metabolism; D012172:Retinaldehyde / Q000494:pharmacology*; D012176:Retinoids / Q000494:pharmacology*; D012995:Solubility; D013449:Sulfonamides; D013481:Superoxides / Q000378:metabolism
D007546:Isoquinolines; D010750:Phosphoproteins; D010879:Piperazines; D012176:Retinoids; D013449:Sulfonamides; D013481:Superoxides; D004533:Egtazic Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D011493:Protein Kinase C; D012172:Retinaldehyde