PMID- 8803956
OWN - NLM
STAT- MEDLINE
DCOM- 19961205
LR  - 20131121
IS  - 0379-0355 (Print)
IS  - 0379-0355 (Linking)
VI  - 18
IP  - 4
DP  - 1996 May
TI  - Inhibition of phosphodiesterase IV and intracellular calcium levels in human 
      polymorphonuclear leukocytes.
PG  - 239-45
AB  - Phosphodiesterase (PDE) isoenzyme type IV is the predominant cyclic AMP 
      hydrolytic activity in polymorphonuclear leukocytes (PMNs). PDE IV inhibitors 
      depress functional responses of PMNs but their influence on intracellular calcium 
      concentration ([Ca2+]i) has not been extensively studied. The present study 
      examined the effects of rolipram (a selective PDE IV inhibitor) on the 
      chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMLP)-induced changes 
      of [Ca2+]i in fura-2 loaded human PMNs. Rolipram (1 nM-10 microM) did not alter 
      basal [Ca2+]i values. fMLP (10 nM approximately EC50) produced a transient 
      calcium response, i.e., a peak followed by decay to a residual value above 
      baseline. Peak [Ca2+]i values after fMLP were not altered but a faster decay and 
      a lower residual [Ca2+]i were observed in rolipram (0.1-10 microM)-treated cells. 
      fMLP added after thimerosal (20 microM) produced a peak followed by a sustained 
      oscillatory response. Rolipram (up to 10 microM) did not alter the peak but 
      inhibited the sustained response (-log IC50 = 6.39 +/- 0.12). The inhibitory 
      effects of rolipram may be due to alterations in the mobilization of Ca2+ 
      produced by the increase in the cellular content of cyclic AMP. SKF94120 (a 
      selective PDE III inhibitor) produced minor effects on the fMLP-induced calcium 
      response. SCA40 (a mixed PDE III/IV/V inhibitor) produced similar effects but was 
      less potent than rolipram. Reduction of the calcium response probably underlies 
      the inhibition of PMN functions produced by PDE IV inhibitors.
FAU - Villagrasa, V
AU  - Villagrasa V
AD  - Department of Pharmacology, Faculty of Medicine and Odontology, University of 
      Valencia, Spain.
FAU - Navarrete, C
AU  - Navarrete C
FAU - Sanz, C
AU  - Sanz C
FAU - Berto, L
AU  - Berto L
FAU - Perpina, M
AU  - Perpina M
FAU - Cortijo, J
AU  - Cortijo J
FAU - Morcillo, E J
AU  - Morcillo EJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Spain
TA  - Methods Find Exp Clin Pharmacol
JT  - Methods and findings in experimental and clinical pharmacology
JID - 7909595
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Imidazoles)
RN  - 0 (Parasympatholytics)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (Pyrazines)
RN  - 0 (Pyrrolidinones)
RN  - 142744-39-6 (6-bromo-8-methylaminoimidazo(1,2-a)pyrazine-2-carbonitrile)
RN  - 2225PI3MOV (Thimerosal)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 89541-55-9 (5-(4-acetamidophenyl)pyrazin-2(1H)-one)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 3.1.4.- (Phosphoric Diester Hydrolases)
RN  - EC 3.1.4.17 (3',5'-Cyclic-AMP Phosphodiesterases)
RN  - EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4)
RN  - K676NL63N7 (Rolipram)
RN  - SY7Q814VUP (Calcium)
RN  - TSN3DL106G (Fura-2)
SB  - IM
MH  - *3',5'-Cyclic-AMP Phosphodiesterases
MH  - Calcium/*metabolism
MH  - Cardiotonic Agents/toxicity
MH  - Cell Survival
MH  - Chemotaxis/drug effects
MH  - Cyclic AMP/metabolism
MH  - Cyclic Nucleotide Phosphodiesterases, Type 4
MH  - Fura-2/chemistry
MH  - Humans
MH  - Imidazoles/toxicity
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/drug effects/*enzymology/metabolism
MH  - Parasympatholytics/toxicity
MH  - Phosphodiesterase Inhibitors/*toxicity
MH  - Phosphoric Diester Hydrolases/*drug effects/metabolism
MH  - Pyrazines/toxicity
MH  - Pyrrolidinones/toxicity
MH  - Rolipram
MH  - Thimerosal/toxicity
EDAT- 1996/05/01 00:00
MHDA- 1996/05/01 00:01
CRDT- 1996/05/01 00:00
PHST- 1996/05/01 00:00 [pubmed]
PHST- 1996/05/01 00:01 [medline]
PHST- 1996/05/01 00:00 [entrez]
PST - ppublish
SO  - Methods Find Exp Clin Pharmacol. 1996 May;18(4):239-45.