PMID- 17406807
OWN - NLM
STAT- MEDLINE
DCOM- 20071109
LR  - 20181201
IS  - 1023-3830 (Print)
IS  - 1023-3830 (Linking)
VI  - 56
IP  - 3
DP  - 2007 Mar
TI  - The inhibitory effects of H+ K+ ATPase inhibitors on human neutrophils in vitro: 
      restoration by a K+ ionophore.
PG  - 105-11
AB  - OBJECTIVE: This study investigated the ability of proton pump inhibitors (PPI), 
      such as omeprazole and pantoprazole, to inhibit neutrophil migration, calcium 
      mobilization and the mechanisms involved in this inhibition. METHODS: Neutrophils 
      were incubated with different concentrations of omeprazole and pantoprazole for 
      30 min and stimulated to migrate with fMLP and IL-8. Treatment toxicity was 
      assessed by MTT assay. The intracellular calcium levels were analyzed in 
      neutrophils pre-treated with omeprazole and pre-loaded with FURA-2AM, when 
      stimulated with fMLP. The activity of p38 MAP Kinase was evaluated by Western 
      blot after treatment with omeprazole. RESULTS: Omeprazole is able to inhibit 
      neutrophil chemotaxis to fMLP and IL-8. Pantoprazole demonstrated the same 
      ability. This inhibitory effect was not due to a toxic effect of the proton pump 
      inhibitors. Inhibition of v-ATPase by bafilomycin did not modify the ability of 
      fMLP or IL-8 to induce neutrophil migration. Omeprazole was also able to decrease 
      intracellular calcium availability. The addition of a potassium ionophore, 
      nigericin, restored the migratory ability, as well as the intracellular calcium 
      levels. The activity of p38 MAP Kinase was decreased in neutrophils pretreated 
      with omeprazole. CONCLUSION: Proton pump inhibitors promote inhibition of H+ K+ 
      ATPase in neutrophils, resulting in cationic flow disturbances through the 
      cellular membrane that, consequently, inhibit migratory and intracellular events 
      such as calcium influx and p38 MAP Kinase activation.
FAU - Martins de Oliveira, R
AU  - Martins de Oliveira R
AD  - Clinical Pharmacology and Gastroenterology Unit, Sao Francisco University Medical 
      School, Av. Sao Francisco de Assis 218, 12916-900, Braganca Paulista, SP, Brazil.
FAU - Antunes, E
AU  - Antunes E
FAU - Pedrazzoli, J Jr
AU  - Pedrazzoli J Jr
FAU - Gambero, A
AU  - Gambero A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Inflamm Res
JT  - Inflammation research : official journal of the European Histamine Research 
      Society ... [et al.]
JID - 9508160
RN  - 0 (2-Pyridinylmethylsulfinylbenzimidazoles)
RN  - 0 (Interleukin-8)
RN  - 0 (Ionophores)
RN  - 0 (Macrolides)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Proton Pump Inhibitors)
RN  - 116764-51-3 (bafilomycin A)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - D8TST4O562 (Pantoprazole)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.6.3.10 (H(+)-K(+)-Exchanging ATPase)
RN  - KG60484QX9 (Omeprazole)
RN  - RRU6GY95IS (Nigericin)
RN  - RWP5GA015D (Potassium)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - 2-Pyridinylmethylsulfinylbenzimidazoles/pharmacology
MH  - Apoptosis/drug effects
MH  - Calcium/metabolism
MH  - Cell Movement/drug effects
MH  - Cells, Cultured
MH  - Gastric Acid/metabolism
MH  - H(+)-K(+)-Exchanging ATPase/metabolism
MH  - Humans
MH  - Interleukin-8/pharmacology
MH  - Ionophores/*pharmacology
MH  - Macrolides/pharmacology
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/cytology/*drug effects/*enzymology
MH  - Nigericin/*pharmacology
MH  - Omeprazole/pharmacology
MH  - Pantoprazole
MH  - Potassium/*metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - *Proton Pump Inhibitors
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2007/04/05 09:00
MHDA- 2007/11/10 09:00
CRDT- 2007/04/05 09:00
PHST- 2007/04/05 09:00 [pubmed]
PHST- 2007/11/10 09:00 [medline]
PHST- 2007/04/05 09:00 [entrez]
AID - 10.1007/s00011-006-6127-6 [doi]
PST - ppublish
SO  - Inflamm Res. 2007 Mar;56(3):105-11. doi: 10.1007/s00011-006-6127-6.