Neurokinin-1 receptor and substance P messenger RNA levels increase during intraabdominal adhesion formation.
BACKGROUND
Intraabdominal peritoneal adhesions are a significant cause of postoperative morbidity and remain one of the major long-term complications associated with abdominal surgery. Adhesion formation at the molecular level involves a complex interaction of cytokines, growth factors, cell adhesion molecules, and neuropeptides, as well as many other factors secreted by cells proximate to the traumatized area. Limited studies exist which investigate the molecular processes involved in adhesion formation. Therefore, the aim of the present study was to determine the pattern of gene expression for substance P, the neurokinin-1 receptor, and downstream mediators of substance P action during the early stages of adhesion formation in the rat.


METHODS
Four ischemic buttons were created on one side of the peritoneum in male Wistar rats. Animals were sacrificed at 3, 6, and 12 h and 1, 3, 5, and 7 days following surgery. Peritoneal tissue from ischemic buttons and from the opposite sidewall was harvested for total RNA isolation. Semiquantitative RT-PCR was used to measure changes at the transcript level for the neurokinin-1 receptor, substance P, TGFbeta-1, and the cell adhesion molecules ICAM-1 and VCAM-1.


RESULTS
Messenger RNA levels for substance P, neurokinin-1 receptor, TGFbeta-1, ICAM-1, and VCAM-1 were significantly increased in peritoneal tissue taken from ischemic button sites (P < 0.05) when compared with controls. In the peritoneal tissues taken from the opposite sidewall, there was a significant (P < 0.05) early increase in substance P mRNA levels. TGF-beta1, neurokinin-1 receptor, and ICAM-1 mRNA levels were also significantly (P < 0.05) increased when compared to controls, while the mRNA levels for VCAM-1 did not change.


CONCLUSIONS
The increased levels of mRNA for substance P, the neurokinin-1 receptor, and the downstream mediators of substance P action, TGF-beta1, ICAM-1, and VCAM-1, in peritoneal tissue associated with intraabdominal adhesions support a role for substance P in adhesion formation.
Reed
Karen L
KL
Department of Surgery, Boston University School of Medicine, Massachusetts 02118, USA.
Fruin
A Brent
AB
Bishop-Bartolomei
Kelly K
KK
Gower
Adam C
AC
Nicolaou
Michael
M
Stucchi
Arthur F
AF
Leeman
Susan E
SE
Becker
James M
JM
D000005:Abdomen / Q000601:surgery; D000818:Animals; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D010537:Peritoneum / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000235:genetics*; D013373:Substance P / Q000235:genetics*; D000267:Tissue Adhesions / Q000503:physiopathology*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D013373:Substance P