Verapamil inhibits in-vitro leucotriene B4 release by rectal mucosa in active ulcerative colitis.
Increased mucosal eicosanoid synthesis occurs in active ulcerative colitis; suppression of the synthesis of pro-inflammatory leucotrienes could be therapeutically useful. Neutrophil 5-lipoxygenase is calcium-dependent. In this study, the effect of the calcium channel antagonist, verapamil, on the release of eicosanoids by colitic rectal mucosal biopsies has been examined. Verapamil in therapeutic concentration (5 micrograms/ml, 10(-5) M) reduced leucotriene B4 release from actively inflamed rectal mucosa by 30% (from 60 (5.0 S.E.M.) ng/g wet weight/20 min without, to 42 (5.7 S.E.M.) with verapamil, P less than 0.05), but had no effect on leucotriene B4 release by rectal biopsies taken from patients with quiescent ulcerative colitis (39 (2.8 S.E.M.) ng/g wet weight/20 min without, and 43 (5.0 S.E.M.) with verapamil). Verapamil did not affect mucosal prostaglandin E2 release. The results suggest that, in active ulcerative colitis, verapamil inhibits mucosal 5-lipoxygenase activity and warrants therapeutic evaluation.
Gertner
D J
DJ
St Mark's Hospital, London, UK.
Rampton
D S
DS
Stevens
T R
TR
Lennard-Jones
J E
JE
D001706:Biopsy; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism*; D012007:Rectum / Q000187:drug effects* / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*
D007975:Leukotriene B4; D014700:Verapamil