Effect of vanilloid drugs on gastrointestinal transit in mice.
1. We have studied the effect of capsaicin, piperine and anandamide, drugs which activate vanilloid receptors and capsazepine, a vanilloid receptor antagonist, on upper gastrointestinal motility in mice. 2. Piperine (0.5 - 20 mg kg(-1) i.p.) and anandamide (0.5 - 20 mg kg(-1) i.p.), dose-dependently delayed gastrointestinal motility, while capsaicin (up to 3 mg kg(-1) i.p.) was without effect. Capsazepine (15 mg kg(-1) i.p.) neither per se affected gastrointestinal motility nor did it counteract the inhibitory effect of both piperine (10 mg kg(-1)) and anandamide (10 mg kg(-1)). 3. A per se non effective dose of SR141716A (0.3 mg kg(-1) i.p.), a cannabinoid CB(1) receptor antagonist, counteracted the inhibitory effect of anandamide (10 mg kg(-1)) but not of piperine (10 mg kg(-1)). By contrast, the inhibitory effect of piperine (10 mg kg(-1)) but not of anandamide (10 mg kg(-1)) was strongly attenuated in capsaicin (75 mg kg(-1) in total, s.c.)-treated mice. 4. Pretreatment of mice with N(G)-nitro-L-arginine methyl ester (25 mg kg(-1) i.p.), yohimbine (1 mg kg(-1), i.p.), naloxone (2 mg kg(-1) i.p.), or hexamethonium (1 mg kg(-1) i.p.) did not modify the inhibitory effect of both piperine (10 mg kg(-1)) and anandamide (10 mg kg(-1)). 5. The present study indicates that the vanilloid ligands anandamide and piperine, but not capsaicin, can reduce upper gastrointestinal motility. The effect of piperine involves capsaicin-sensitive neurones, but not vanilloid receptors, while the effect of anandamide involves cannabinoid CB(1), but not vanilloid receptors.
Izzo
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AA
Department of Experimental Pharmacology, University of Naples 'Federico II', Naples, Italy. aaizzo@unina.it
Capasso
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R
Pinto
L
L
Di Carlo
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G
Mascolo
N
N
Capasso
F
F
D000470:Alkaloids; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D052117:Benzodioxoles; D002211:Capsaicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D005772:Gastrointestinal Transit / Q000187:drug effects*; D018738:Hexamethonium / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D011955:Receptors, Drug / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D015016:Yohimbine / Q000494:pharmacology
D000470:Alkaloids; D001095:Arachidonic Acids; D052117:Benzodioxoles; D063388:Endocannabinoids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D011955:Receptors, Drug; D015016:Yohimbine; D009270:Naloxone; D018738:Hexamethonium; D000077285:Rimonabant; D002211:Capsaicin; C008922:piperine; C078814:anandamide; D019331:NG-Nitroarginine Methyl Ester