PMID- 8866334
OWN - NLM
STAT- MEDLINE
DCOM- 19970304
LR  - 20190710
IS  - 0022-3573 (Print)
IS  - 0022-3573 (Linking)
VI  - 48
IP  - 7
DP  - 1996 Jul
TI  - Synergistic inhibition of human polymorphonuclear function by prostaglandin E1 
      and linsidomine.
PG  - 706-11
AB  - Polymorphonuclear cells (PMN) are the dominating inflammatory cell population in 
      acute tissue injury and contribute to host-defence mechanisms by formation and 
      release of chemical mediators. The aim of the present study was to investigate 
      whether chemoattractant-induced PMN stimulation can be synergistically 
      antagonized by vasodilatory prostaglandins and nitric oxide (NO), both being 
      formed by the vasculature in inflamed areas. PGE1 (10 nM-10 microM) inhibited 
      concentration-dependently formyl-methionyl-leucyl-phenylalanine (fMLP)-induced 
      beta-glucuronidase and oxygen radical (O2.) release from human PMN. The NO donor 
      linsidomine (100 microM) was ineffective, but significantly enhanced PGE1 effects 
      on oxygen radical generation and enzyme release. The non-selective 
      phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine (IBMX) (0.5 mM) 
      potentiated PGE1 effects on all parameters measured. The combination linsidomine 
      (100 microM) plus IBMX (0.5 mM) did not additionally reduce beta-glucuronidase 
      release, but abolished fMLP-stimulated O2. generation. There was a stimulation of 
      cAMP formation by PGE1 but not by linsidomine, both in the absence and presence 
      of IBMX. It is concluded that the effects of linsidomine on PMN function and its 
      synergism with PGE1 are not tightly correlated with total cAMP accumulation. 
      Alternatively, the inhibition of O2. generation by linsidomine may be related to 
      its ability to modulate the activation of the NADPH oxidase system or to scavenge 
      free oxygen radicals.
FAU - Gladis-Villanueva, M
AU  - Gladis-Villanueva M
AD  - Institut fur Pharmakologie, Heinrich-Heine-Universitat Dusseldorf, Germany.
FAU - Schror, K
AU  - Schror K
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pharm Pharmacol
JT  - The Journal of pharmacy and pharmacology
JID - 0376363
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 5O5U71P6VQ (linsidomine)
RN  - D46583G77X (Molsidomine)
RN  - E0399OZS9N (Cyclic AMP)
RN  - F5TD010360 (Alprostadil)
RN  - TBT296U68M (1-Methyl-3-isobutylxanthine)
SB  - IM
MH  - 1-Methyl-3-isobutylxanthine/pharmacology
MH  - Alprostadil/*pharmacology
MH  - Cyclic AMP/*metabolism
MH  - Drug Synergism
MH  - Humans
MH  - Molsidomine/*analogs & derivatives/pharmacology
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/*drug effects/metabolism
MH  - Phosphodiesterase Inhibitors/pharmacology
MH  - Platelet Aggregation Inhibitors/*pharmacology
MH  - Respiratory Burst/*drug effects
EDAT- 1996/07/01 00:00
MHDA- 1996/07/01 00:01
CRDT- 1996/07/01 00:00
PHST- 1996/07/01 00:00 [pubmed]
PHST- 1996/07/01 00:01 [medline]
PHST- 1996/07/01 00:00 [entrez]
AID - 10.1111/j.2042-7158.1996.tb03956.x [doi]
PST - ppublish
SO  - J Pharm Pharmacol. 1996 Jul;48(7):706-11. doi: 
      10.1111/j.2042-7158.1996.tb03956.x.