PMID- 12374895
OWN - NLM
STAT- MEDLINE
DCOM- 20030714
LR  - 20190916
IS  - 0920-3206 (Print)
IS  - 0920-3206 (Linking)
VI  - 16
IP  - 3
DP  - 2002 May
TI  - Impaired mechanisms of leukocyte adhesion in vitro by the calcium channel 
      antagonist mibefradil.
PG  - 183-93
AB  - PURPOSE: Enhanced adhesion to the vascular endothelium and excessive trafficking 
      to extravascular locations can lead to serious tissue injury and destruction. 
      Therefore, interfering with molecular mechanisms of leukocyte adhesion to the 
      vascular endothelium is an important goal to block diseases like chronic 
      inflammations and atherosclerosis. METHODS: We studied the influence of the 
      calcium antagonists mibefradil (T-type channel blocker), amlodipine and verapamil 
      (both L-type channel blockers) on mechanisms related to leukocyte adhesion using 
      isolated peripheral human blood leukocytes. RESULTS: Mibefradil but not 
      amlodipine and verapamil attenuated leukocyte adhesion in vitro. Regarding the 
      mechanisms we found that mibefradil reduced the surface expression of beta2 
      integrins and L-selectin. The immobilization of the beta2 integrin subunit to the 
      cytoskeleton that was inducible by receptor cross linking was impaired. 
      Mibefradil was able to significantly inhibit the 
      formyl-methionyl-leucyl-phenylalanine (fMLP) induced calcium rise, which suggests 
      that mibefradil interfered with integrin signaling through blocking the 
      intracellular calcium rise. SK&F 96365, a blocker of the capacitative calcium 
      entry had no effect on cell adhesion and was less effective to influence integrin 
      mediated mechanisms than mibefradil. CONCLUSION: Our data suggest that mibefradil 
      or chemically related substances are promising to serve as potent drugs to 
      prevent excessive adhesion of leukocytes.
FAU - Nebe, Barbara
AU  - Nebe B
AD  - Department of Internal Medicine, University of Rostock, Ernst-Heydemann-Strasse 
      6, 18055 Rostock, Germany.
FAU - Holzhausen, Christian
AU  - Holzhausen C
FAU - Rychly, Joachim
AU  - Rychly J
FAU - Urbaszek, Wilhelm
AU  - Urbaszek W
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cardiovasc Drugs Ther
JT  - Cardiovascular drugs and therapy
JID - 8712220
RN  - 0 (CD18 Antigens)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Calcium Channels, T-Type)
RN  - 126880-86-2 (L-Selectin)
RN  - 1J444QC288 (Amlodipine)
RN  - 27B90X776A (Mibefradil)
RN  - CJ0O37KU29 (Verapamil)
RN  - SY7Q814VUP (Calcium)
SB  - IM
CIN - Cardiovasc Drugs Ther. 2002 May;16(3):179-80. PMID: 12374893
MH  - Adult
MH  - Amlodipine/pharmacology
MH  - CD18 Antigens/metabolism
MH  - Calcium/metabolism
MH  - Calcium Channel Blockers/*pharmacology
MH  - Calcium Channels, L-Type/drug effects
MH  - Calcium Channels, T-Type/drug effects
MH  - Cell Adhesion/drug effects
MH  - Cells, Cultured
MH  - Cytoskeleton/metabolism
MH  - Female
MH  - Flow Cytometry
MH  - Granulocytes/drug effects/metabolism/physiology
MH  - Humans
MH  - L-Selectin/metabolism
MH  - Leukocytes/*drug effects/metabolism/physiology
MH  - Male
MH  - Mibefradil/*pharmacology
MH  - Microscopy, Confocal
MH  - Verapamil/pharmacology
EDAT- 2002/10/11 04:00
MHDA- 2003/07/15 05:00
CRDT- 2002/10/11 04:00
PHST- 2002/10/11 04:00 [pubmed]
PHST- 2003/07/15 05:00 [medline]
PHST- 2002/10/11 04:00 [entrez]
AID - 5100182 [pii]
AID - 10.1023/a:1020688019792 [doi]
PST - ppublish
SO  - Cardiovasc Drugs Ther. 2002 May;16(3):183-93. doi: 10.1023/a:1020688019792.