PMID- 2555342
OWN - NLM
STAT- MEDLINE
DCOM- 19900108
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 264
IP  - 34
DP  - 1989 Dec 5
TI  - Chemotactic peptide induces cAMP elevation in human neutrophils by amplification 
      of the adenylate cyclase response to endogenously produced adenosine.
PG  - 20177-80
AB  - The transient increase in human neutrophil cAMP levels induced by the 
      chemoattractant N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) is shown to 
      be caused by amplification of adenylate cyclase response to endogenously produced 
      adenosine. The FMLP-stimulated increase in neutrophil cAMP was potentiated 
      markedly by a nonmethylxanthine cAMP phosphodiesterase inhibitor (Ro 20-1724). By 
      inhibiting the degradation of newly formed cAMP, Ro 20-1724 rendered the 
      FMLP-induced cAMP elevation persistent rather than transient. The role of 
      endogenously produced adenosine in this phenomenon is demonstrated by the ability 
      of either adenosine deaminase or theophylline, an adenosine receptor antagonist, 
      to prevent FMLP-stimulated cAMP elevation. The general nature of the 
      FMLP-potentiated cAMP response is indicated by the finding that FMLP-treated 
      neutrophils, in the presence of exogenously supplied adenosine deaminase, 
      exhibited augmented cAMP generation in response to three different types of 
      receptor agonists: 2-chloroadenosine, prostaglandin E1, and L-isoproterenol. 
      Moreover, like the neutrophil cAMP increase caused by FMLP alone, the ability of 
      FMLP to augment cAMP response to 2-chloroadenosine in adenosine deaminase-treated 
      cells was short-lived and declined after 1.0 min of exposure to FMLP. 
      Preincubation of neutrophil suspensions with the adenylate cyclase inhibitor SQ 
      22,536 completely prevented FMLP-induced cAMP generation. Furthermore, when 
      neutrophil suspensions were preincubated with concentrations of Ro 20-1724, which 
      apparently maximally inhibit cAMP phosphodiesterase, a 30-s incubation with FMLP 
      still resulted in substantially elevated cAMP levels. It therefore appears that 
      FMLP raises cAMP by activating adenylate cyclase rather than inhibiting cAMP 
      phosphodiesterase.
FAU - Iannone, M A
AU  - Iannone MA
AD  - Division of Experimental Therapy, Burroughs Wellcome Co., Research Triangle Park, 
      North Carolina 27709.
FAU - Wolberg, G
AU  - Wolberg G
FAU - Zimmerman, T P
AU  - Zimmerman TP
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 3.5.4.4 (Adenosine Deaminase)
RN  - EC 4.6.1.1 (Adenylyl Cyclases)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/*blood/physiology
MH  - Adenosine Deaminase/pharmacology
MH  - Adenylyl Cyclases/*blood
MH  - Cyclic AMP/*blood
MH  - Humans
MH  - In Vitro Techniques
MH  - Kinetics
MH  - N-Formylmethionine Leucyl-Phenylalanine/*pharmacology
MH  - Neutrophils/drug effects/*metabolism
EDAT- 1989/12/05 00:00
MHDA- 1989/12/05 00:01
CRDT- 1989/12/05 00:00
PHST- 1989/12/05 00:00 [pubmed]
PHST- 1989/12/05 00:01 [medline]
PHST- 1989/12/05 00:00 [entrez]
AID - S0021-9258(19)47042-7 [pii]
PST - ppublish
SO  - J Biol Chem. 1989 Dec 5;264(34):20177-80.