PMID- 1662948
OWN - NLM
STAT- MEDLINE
DCOM- 19920220
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 42 Suppl
DP  - 1991 Dec 11
TI  - Ca2+ ionophore-induced cyclic adenosine-3',5'-monophosphate elevation in human 
      neutrophils. A calmodulin-dependent potentiation of adenylate cyclase response to 
      endogenously produced adenosine: comparison to chemotactic agents.
PG  - S105-11
AB  - The cyclic adenosine-3',5'-monophosphate (cAMP) elevation caused by exposure of 
      human neutrophils to the Ca2+ ionophore A23187 was prevented when endogenously 
      produced adenosine was either removed by preincubation with adenosine deaminase 
      or blocked from binding to the adenosine receptor by antagonists [theophylline or 
      (E)-4-(1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxo-9H-purin-8-yl)cinnamic acid]. In 
      the absence of endogenous adenosine, A23187 potentiated the neutrophil cAMP 
      response to 2-chloroadenosine, prostaglandin E1, and isoproterenol. When 
      neutrophil suspensions were preincubated with concentrations of Ro 20-1724, which 
      appeared to maximally inhibit cAMP phosphodiesterase, A23187 was still able to 
      substantially elevate cAMP levels, suggesting that A23187 increases cAMP by 
      amplifying adenylate cyclase responsiveness to the agonist rather than by 
      inhibiting cAMP phosphodiesterase. The ability of A23187 to augment the cAMP 
      elevation caused by 2-chloroadenosine was persistent over a 10-min period. The 
      neutrophil cAMP elevations caused by chemoattractants leukotriene B4, C5a, and 
      N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) were all prevented when 
      endogenously produced adenosine was eliminated from the cell suspensions by the 
      addition of adenosine deaminase. The A23187-induced cAMP elevation was inhibited 
      completely by the calmodulin inhibitors chlorpromazine, trifluoperazine and 
      N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, whereas cAMP levels induced 
      by FMLP, leukotriene B4 and C5a were less affected. It appears that A23187 raises 
      cAMP in human neutrophils by a calmodulin-dependent potentiation of adenylate 
      cyclase responsiveness to endogenously produced adenosine while the 
      chemoattractant-induced cAMP elevations (FMLP), leukotriene B4, and C5a), 
      although possibly Ca2+ dependent, are less sensitive to calmodulin inhibitors and 
      may involve additional biochemical events.
FAU - Iannone, M A
AU  - Iannone MA
AD  - Division of Experimental Therapy, Wellcome Research Laboratories, Research 
      Triangle Park, NC 27709.
FAU - Wolberg, G
AU  - Wolberg G
FAU - Zimmerman, T P
AU  - Zimmerman TP
LA  - eng
PT  - Journal Article
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Calmodulin)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 146-77-0 (2-Chloroadenosine)
RN  - 1HGW4DR56D (Leukotriene B4)
RN  - 37H9VM9WZL (Calcimycin)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 80295-54-1 (Complement C5a)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 4.6.1.1 (Adenylyl Cyclases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - 2-Chloroadenosine/pharmacology
MH  - Adenylyl Cyclases/*metabolism
MH  - Calcimycin/*pharmacology
MH  - Calcium/metabolism
MH  - Calmodulin/antagonists & inhibitors
MH  - Complement C5a/pharmacology
MH  - Cyclic AMP/biosynthesis/*metabolism
MH  - Drug Interactions
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - Leukotriene B4/pharmacology
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/*drug effects/metabolism
MH  - Phosphodiesterase Inhibitors/pharmacology
MH  - Radioimmunoassay
MH  - Time Factors
EDAT- 1991/12/11 00:00
MHDA- 1991/12/11 00:01
CRDT- 1991/12/11 00:00
PHST- 1991/12/11 00:00 [pubmed]
PHST- 1991/12/11 00:01 [medline]
PHST- 1991/12/11 00:00 [entrez]
AID - 0006-2952(91)90399-P [pii]
AID - 10.1016/0006-2952(91)90399-p [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1991 Dec 11;42 Suppl:S105-11. doi: 
      10.1016/0006-2952(91)90399-p.