Octreotide acts on anorectal physiology: a dynamic study in healthy subjects.
BACKGROUND
Somatostatin is localized in the intestinal and pelvic nerves of the anorectum and it seems to act as an important neurotransmitter. However, previous analyses of octreotide (a somatostatin analog) effects on anal function showed conflicting results. By use of a dynamic model in healthy subjects, with comparison to the myogenic effect of glucagon, the aim of our study was to further investigate the pharmacologic targets of octreotide.


METHODS
This was a placebo-controlled, randomized, double-blinded crossover study performed in 12 healthy volunteers who received octreotide, glucagon, or placebo intravenously on separate days. During each sequence, several pressure steps in 3 different protocols of rectal isobaric distension were applied with an electronic barostat. Manometric responses of the anal canal, adaptative volumes, and perception scores of the rectum were recorded.


RESULTS
During both phasic and stepwise distensions, a significant drug effect was encountered at the anal level. Compared with placebo, octreotide significantly increased pressures at both upper and lower levels of the anal canal. In contrast, glucagon decreased pressures at the upper part of the anal canal. Octreotide significantly decreased rectal volumes to phasic distension, but glucagon did not induce any change on rectal adaptation. In addition, neither drug modified perception scores.


CONCLUSIONS
This study suggests that octreotide acts on reflex arcs and rectal myenteric neurons rather than on anal myogenic targets that respond to glucagon.
Siproudhis
L
L
Gastroenterology Unit, Hôpital Pontchaillou, Rennes, France.
Bellissant
E
E
Juguet
F
F
Allain
H
H
Bretagne
J F
JF
Gosselin
M
M
D000328:Adult; D001003:Anal Canal / Q000187:drug effects* / Q000502:physiology; D000704:Analysis of Variance; D000930:Antidiarrheals / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005934:Glucagon / Q000494:pharmacology; D006801:Humans; D008297:Male; D008365:Manometry; D008875:Middle Aged; D015282:Octreotide / Q000494:pharmacology*; D011312:Pressure; D012007:Rectum / Q000187:drug effects* / Q000502:physiology; D012016:Reference Values
D000930:Antidiarrheals; D005765:Gastrointestinal Agents; D005934:Glucagon; D015282:Octreotide