Effects of long-term treatment with anthranoids and sodium picosulphate on the contents of vasoactive intestinal polypeptide, somatostatin and substance P in the rat colon.
OBJECTIVE
To examine the effects of chronic treatment and a single high-dose application of anthranoids and sodium picosulphate on the neuropeptide content of the rat colon.


METHODS
Over a 6-month period, eight groups of rats were each given one of the following: sennosides or sodium picosulphate in low daily doses (10 and 2.5 mg/kg/day, respectively), in high daily doses (40 and 10 mg/kg/day, respectively), and in high twice-weekly doses (30 and 7.5 mg/kg/day, respectively); high daily doses of danthron (500 mg/kg/day); and vehicle (tragacanth 0.5%) only. Four further groups of rats each received a single dose of vehicle or a high dose of one of the three laxatives. All rats were killed 48 h after the last dose. The ascending and descending colon were removed and separated into mucosa, submucosa, and muscularis externa. Vasoactive intestinal polypeptide (VIP), somatostatin, and substance P were extracted by boiling and homogenizing the tissue in acetic acid, and their levels were determined using validated radioimmunoassays.


RESULTS
After long-term treatment with high doses of sennosides and danthron, but not after a single high-dose administration, there was a significant reduction in mucosal levels of VIP and somatostatin and in submucosal levels of somatostatin of both colonic segments, as well as in the level of VIP in the muscularis externa of the descending colon. Substance P levels remained unaffected. Sodium picosulphate had no effect.


CONCLUSIONS
Chronic treatment with anthranoids in high doses, but not with sodium picosulphate, reduces VIP and somatostatin levels in the rat colon. This may represent damage to the enteric nervous tissue or a pharmacological effect of the anthranoids, causing decreased synthesis or increased breakdown of these peptides.
Tzavella
K
K
Medizinische Klinik, University of Munich, Germany.
Schenkirsch
G
G
Riepl
R L
RL
Odenthal
K P
KP
Leng-Peschlow
E
E
Müller-Lissner
S A
SA
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D002400:Cathartics / Q000494:pharmacology*; D002951:Citrates; D003106:Colon / Q000378:metabolism*; D005260:Female; D009479:Neuropeptides / Q000378:metabolism*; D009942:Organometallic Compounds; D010847:Picolines / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D012676:Senna Extract / Q000494:pharmacology*; D013004:Somatostatin / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D000880:Anthraquinones; D002400:Cathartics; D002951:Citrates; D009479:Neuropeptides; D009942:Organometallic Compounds; D010847:Picolines; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D012676:Senna Extract; C005701:picosulfate sodium; C004315:danthron