Calcitonin gene-related peptide and substance P decrease in the rabbit colon during colitis. A time study.
The sensory neuropeptides, substance P and calcitonin gene-related peptide, have been implicated in inflammatory reactions in several tissues. An immune-complex model of colitis was used in rabbits to determine the colonic content (nmol/g protein) of immunoreactive substance P and calcitonin gene-related peptide at various times after induction of inflammation to assess changes in these neuropeptides during the inflammatory response. Calcitonin gene-related peptide content was decreased by 66% 4 hours after induction of inflammation and reached a maximum of 80% at 48 hours. The substance P content was decreased at 8 hours, with a maximum decrease of 64% at 48 hours. Substance P decrease was detected in the muscle layer. The amounts of substance P in the mucosal/submucosal layer extracts were too low to allow accurate measurements. Calcitonin gene-related peptide decreased both in the muscle and the mucosal-submucosal layers. Immunohistochemical analysis showed that calcitonin gene-related peptide and substance P innervation patterns were comparable in normal and inflamed colon, even though there appeared to be a decrease in density and intensity of the staining, particularly for calcitonin gene-related peptide at 48 hours. The early decrease of calcitonin gene-related peptide and substance P during the time course of colitis might be due to release from nerve terminals of the gut during the inflammatory response. The profound changes in colonic calcitonin gene-related peptide and substance P content during colitis may have important implications during inflammation and subsequent tissue repair and may also lead to disturbances in gut motility.
Eysselein
V E
VE
Inflammatory Bowel Disease Center, Harbor-UCLA Medical Center, Torrance.
Reinshagen
M
M
Cominelli
F
F
Sternini
C
C
Davis
W
W
Patel
A
A
Nast
C C
CC
Bernstein
D
D
Anderson
K
K
Khan
H
H
D000818:Animals; D000936:Antigen-Antibody Complex; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis*; D003092:Colitis / Q000139:chemically induced / Q000473:pathology; D003106:Colon / Q000737:chemistry* / Q000294:innervation / Q000473:pathology; D005557:Formaldehyde; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000737:chemistry / Q000473:pathology; D008297:Male; D009412:Nerve Fibers / Q000737:chemistry; D009474:Neurons / Q000737:chemistry; D011817:Rabbits; D013373:Substance P / Q000032:analysis*; D013997:Time Factors
D000936:Antigen-Antibody Complex; D005557:Formaldehyde; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide