Concentration-dependent dual effect of anandamide on sensory neuropeptide release from isolated rat tracheae.
Most actions of anandamide (AEA) are mediated by the cannabinoid 1 (CB(1)) receptor activation, but on sensory neurones it is also an agonist on the vanilloid subtype 1 receptor (VR(1)). The aim of the present study was to analyse the effect of AEA (10(-6)-10(-4) M) on inhibitory CB(1) and excitatory VR(1) receptors by measuring sensory neuropeptide release such as somatostatin, substance P and calcitonin gene-related peptide, from isolated rat tracheae. AEA (10(-6) M) vas without significant effect, 10(-5) M inhibited neuropeptide release, which was abolished by the G protein-coupled receptor blocker pertussis toxin (100 ng/ml) and the CB(1) receptor antagonist SR141716A (5x10(-7) M). High concentrations of AEA (5x10(-5) M, 10(-4) M) increased the release of the peptides and this inhibition was prevented by the competitive VR(1) antagonist capsazepine (10(-5) M). These results indicate a dual, concentration-dependent action of AEA on CB(1) receptors and VR(1) on peripheral sensory nerve terminals.
Németh
József
J
Neuropharmacology Research Group of the Hungarian Academy of Sciences, H-7643 PO Box 99, Pécs, Hungary.
Helyes
Zsuzsanna
Z
Thán
Márta
M
Jakab
Balázs
B
Pintér
Erika
E
Szolcsányi
János
J
D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage* / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D066298:In Vitro Techniques; D008297:Male; D009479:Neuropeptides / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin / Q000378:metabolism / Q000494:pharmacology; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists*; D012016:Reference Values; D015203:Reproducibility of Results; D000077285:Rimonabant; D012680:Sensitivity and Specificity; D013004:Somatostatin / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
D001095:Arachidonic Acids; D063388:Endocannabinoids; D009479:Neuropeptides; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013373:Substance P; D013004:Somatostatin; D037342:Pertussis Toxin; D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D000077285:Rimonabant; D002211:Capsaicin; C078814:anandamide