Effect of platelet-activating factor and its antagonists on colonic dysmotility and tissue levels of colonic neuropeptides.
We investigated whether platelet-activating factor (PAF) alters colonic tissue levels of substance P and vasoactive intestinal peptide (VIP), two neuropeptides that regulate colonic motility. Left colons were harvested from NZ White Rabbits and underwent vascular perfusion via the inferior mesenteric artery. Strain gauge transducers were sewn onto the serosal surface of the colon to evaluate colonic motility. Colons were perfused with either buffered saline alone or with 5.0 x 10(-5) M PAF. PAF administration increased tissue VIP and substance P levels and decreased the force of colonic contractions. Pretreatment with WEB-2170 or alprazolam decreased concentrations of both tissue neuropeptides, and decreased the force of colonic contractions and minute motility index. These results suggest that both VIP and substance P are stimulated by PAF and may participate in colonic dysmotility during inflammatory states.
Deshpande
Y
Y
Department of Surgery, St. Louis University School of Medicine, MO.
Longo
W E
WE
Chandel
B
B
Niehoff
M
M
Robinson
S
S
Polities
G
G
Vernava
A M
AM
Kaminski
D L
DL
D000525:Alprazolam / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000503:physiopathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D009479:Neuropeptides / Q000378:metabolism* / Q000502:physiology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011817:Rabbits; D013373:Substance P / Q000378:metabolism / Q000502:physiology; D014230:Triazoles / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000502:physiology
D001381:Azepines; D007457:Iodine Radioisotopes; D009479:Neuropeptides; D010972:Platelet Activating Factor; D014230:Triazoles; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; C063964:bepafant; D000525:Alprazolam