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The Contractile Effect of Anandamide in the Guinea‐Pig Small Intestine is Mediated by Prostanoids but not TRPV 1 Receptors or Capsaicin‐Sensitive Nerves
Author(s) -
Dékány András,
Benko Rita,
Szombati Veronika,
Bartho Lorand
Publication year - 2013
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12041
Subject(s) - anandamide , chemistry , capsaicin , cannabinoid , endocannabinoid system , cannabinoid receptor , trpv1 , pharmacology , hexamethonium , endocrinology , medicine , receptor , antagonist , biology , biochemistry , transient receptor potential channel
Although exogenous and endogenous cannabinoid receptor agonists have well‐documented inhibitory effects on gastrointestinal motility, a TRPV 1 receptor‐mediated excitatory action of anandamide (arachidonoyl ethanolamide, AEA ) in the guinea‐pig ileum strip has also been described. We used in vitro capsaicin desensitization for assessing the possible participation of sensory neurons in the contractile effect of anandamide on the guinea‐pig whole ileum, as well as autonomic drugs and a cyclooxygenase inhibitor for characterizing this response. Isolated organ experiments were used with isotonic recording. Contractions induced by anandamide (1 or 10 μM) were strongly inhibited by tetrodotoxin, indomethacin or atropine plus a tachykinin NK 1 receptor antagonist, but weakly to moderately reduced by atropine alone and partly diminished by the fatty acid amide hydrolase inhibitor URB 597. Neither capsaicin pre‐treatment nor the TRPV1 receptor antagonist BCTC, the ganglionic blocking drug hexamethonium or cannabinoid (CB 1 or CB 2 ) receptor antagonists, influenced the effect of anandamide. It is concluded that the capsaicin‐insensitive, neuronal excitatory effect of anandamide in the intestine is most probably mediated by cyclooxygenase products. Such a mechanism may also play a role at other sites in the mammalian body.