Neural contractions in colonic strips from patients with diverticular disease: role of endocannabinoids and substance P
1. Gut. 2006 Jul;55(7):946-53. doi: 10.1136/gut.2005.076372. Epub 2006 Jan 19.
Neural contractions in colonic strips from patients with diverticular disease:
role of endocannabinoids and substance P.
Guagnini F(1), Valenti M, Mukenge S, Matias I, Bianchetti A, Di Palo S, Ferla G,
Di Marzo V, Croci T.
Author information:
(1)Sanofi-Midy Research Centre, Sanofi-Aventis, Via GB Piranesi 38, 20137 Milan,
Italy.
BACKGROUND AND AIMS: Diverticulosis is a common disease of not completely
defined pathogenesis. Motor abnormalities of the intestinal wall have been
frequently described but very little is known about their mechanisms. We
investigated in vitro the neural response of colonic longitudinal muscle strips
from patients undergoing surgery for complicated diverticular disease
(diverticulitis).
METHODS: The neural contractile response to electrical field stimulation of
longitudinal muscle strips from the colon of patients undergoing surgery for
colonic cancer or diverticulitis was challenged by different receptor agonists
and antagonists.
RESULTS: Contractions of colonic strips from healthy controls and diverticulitis
specimens were abolished by atropine. The beta adrenergic agonist (-)
isoprenaline and the tachykinin NK1 receptor antagonist SR140333 had similar
potency in reducing the electrical twitch response in controls and diseased
tissues, while the cannabinoid receptor agonist (+)WIN 55,212-2 was 100 times
more potent in inhibiting contractions in controls (IC50 42 nmol/l) than in
diverticulitis strips. SR141716, a selective antagonist of the cannabinoid CB1
receptor, had no intrinsic activity in control preparations but potentiated the
neural twitch in diseased tissues by up to 196% in a concentration dependent
manner. SR141716 inhibited (+)WIN 55,212-2 induced relaxation in control strips
but had no efficacy on (+)WIN 55,212-2 responses in strips from diverticular
disease patients. Colonic levels of the endogenous ligand of cannabinoid and
vanilloid TRPV1 receptors anandamide were more than twice those of control
tissues (54 v 27 pmol/g tissue). The axonal conduction blocker tetrodotoxin had
opposite effects in the two preparations, completely inhibiting the contractions
of control strips but potentiating those in diverticular preparations, an effect
selectively inhibited by SR140333.
CONCLUSIONS: Neural control of colon motility is profoundly altered in patients
with diverticulitis. Their raised levels of anandamide, apparent desensitisation
of the presynaptic neural cannabinoid CB1 receptor, and the SR141716 induced
intrinsic response, suggest that endocannabinoids may be involved in the
pathophysiology of complications of colonic diverticular disease.
DOI: 10.1136/gut.2005.076372
PMCID: PMC1856307
PMID: 16423891 [Indexed for MEDLINE]
Conflict of interest statement: Conflict of interest: None declared.