PMID- 1847376
OWN - NLM
STAT- MEDLINE
DCOM- 19910327
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 266
IP  - 6
DP  - 1991 Feb 25
TI  - Cyclic AMP-elevating agents block chemoattractant activation of diradylglycerol 
      generation by inhibiting phospholipase D activation.
PG  - 3498-504
AB  - Agents which elevate cellular cAMP (prostaglandin E2, theophylline, and 
      forskolin) or mimic cAMP action (dibutyryl cAMP) are known to inhibit human 
      neutrophil activation (superoxide generation and secretion) by receptor-linked 
      agonists such as formyl-methionyl-leucyl-phenylalanine (fMLP). Herein, we show 
      that these agents also markedly inhibit fMLP-stimulated diradylglycerol 
      generation (assayed by mass methods). The magnitude of inhibition correlated with 
      the ability of a given agent or combination of agents to elevate cAMP. Both 
      1,2-diacylglycerol and 1-O-alkyl,2-acyl glycerol generation were affected. 
      Effects on the latter species, as well as a lack of effect on fMLP-stimulated 
      inositol phosphate release, implied that cAMP affected diradylglycerol generation 
      from a source other than phospholipase C-dependent phosphoinositide hydrolysis, 
      since phosphatidylinositols do not contain appreciable quantities of the 
      1-O-alkyl linkage. In cells in which the phosphatidylcholine pool was prelabeled 
      using 1-O-[3H]octadecyl-2-lyso-sn-glycero-3-phosphocholine, prostaglandin E2 plus 
      theophylline inhibited the fMLP-activated rapid generation of [3H]phosphatidic 
      acid and its subsequent conversion to [3H]diradylglycerol, implying an effect at 
      the level of phospholipase D. In the presence of ethanol, the fMLP-activated 
      transphosphatidylation of [3H]phosphatidylcholine to generate 
      [3H]phosphatidylethanol (a phospholipase D-dependent reaction) was also markedly 
      inhibited. In contrast, when phorbol 12-myristate 13-acetate was used to activate 
      cells, cAMP-related agents had no effect on phospholipase D activity, 
      diradylglycerol generation, or superoxide generation. The data indicate an 
      inhibitory effect of cyclic AMP on receptor-mediated phospholipase D activation 
      at a site proximal to phospholipase D (e.g., the receptor or G protein). These 
      studies provide a new example of "cross-talk" among signal transduction systems.
FAU - Tyagi, S R
AU  - Tyagi SR
AD  - Department of Biochemistry, Emory University Medical School, Atlanta, Georgia 
      30322.
FAU - Olson, S C
AU  - Olson SC
FAU - Burnham, D N
AU  - Burnham DN
FAU - Lambeth, J D
AU  - Lambeth JD
LA  - eng
GR  - CA46508/CA/NCI NIH HHS/United States
GR  - T32 DK07298/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Chemotactic Factors)
RN  - 0 (Diglycerides)
RN  - 11062-77-4 (Superoxides)
RN  - 1F7A44V6OU (Colforsin)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 82231-61-6 (diarachidonyl diglyceride)
RN  - C137DTR5RG (Theophylline)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 3.1.4.4 (Phospholipase D)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Chemotactic Factors/*pharmacology
MH  - Colforsin/pharmacology
MH  - Cyclic AMP/*metabolism
MH  - Diglycerides/*biosynthesis
MH  - Dinoprostone/pharmacology
MH  - Enzyme Activation
MH  - Humans
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/drug effects/enzymology
MH  - Phospholipase D/*antagonists & inhibitors
MH  - Stimulation, Chemical
MH  - Superoxides
MH  - Theophylline/pharmacology
EDAT- 1991/02/25 00:00
MHDA- 1991/02/25 00:01
CRDT- 1991/02/25 00:00
PHST- 1991/02/25 00:00 [pubmed]
PHST- 1991/02/25 00:01 [medline]
PHST- 1991/02/25 00:00 [entrez]
AID - S0021-9258(19)67823-3 [pii]
PST - ppublish
SO  - J Biol Chem. 1991 Feb 25;266(6):3498-504.