Ca2+ channel blockade by verapamil inhibits GMCs and diarrhea during small intestinal inflammation.
The aim of this study was to investigate whether the blockade of L-type Ca2+ channels with verapamil suppresses giant migrating contractions (GMCs) and therefore diarrhea during small intestinal inflammation. Small intestinal inflammation was induced by infection with the nematode Trichinella spiralis. T. spiralis infection alone significantly increased the frequency of GMCs and decreased the frequency of phase III activity in the small intestine for 9 days. The increased frequency of GMCs was associated with diarrhea. Immunohistochemical staining with specific antibodies indicated that the number of neutrophils and mast cells increased significantly in the jejunal lamina propria during T. spiralis infection. Only the neutrophils increased significantly in the muscularis externa of the jejunum. Myeloperoxidase (MPO) activity increased significantly in the jejunal and ileal lamina propria. Daily verapamil administration during T. spiralis infection significantly reduced the frequency of GMCs and diarrhea but had no further significant effect on the already reduced frequency of phase III activity. Verapamil administration, however, did not reduce MPO activity or immunocyte infiltration in the jejunum or ileum. We conclude that blockade of L-type Ca2+ channels selectively reduces the frequency of GMCs and therefore diarrhea during small intestinal inflammation. The decreased frequency of GMCs is not secondary to a reduction in the inflammatory response.
Lee
C W
CW
Department of Surgery, Medical College of Wisconsin and Zablocki Veterans Affairs Medical Center, Milwaukee 53226, USA.
Sarna
S K
SK
Singaram
C
C
Casper
M A
MA
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology; D020746:Calcium Channels, L-Type; D003967:Diarrhea / Q000517:prevention & control*; D004285:Dogs; D007249:Inflammation; D007411:Intestinal Diseases, Parasitic / Q000503:physiopathology*; D007421:Intestine, Small / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D008407:Mast Cells / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D016065:Myoelectric Complex, Migrating / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D013997:Time Factors; D017160:Trichinella spiralis; D014235:Trichinellosis / Q000503:physiopathology*; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D014700:Verapamil