Opposing effects of cannabinoids and vanilloids on evoked quantal release at the frog neuromuscular junction.
Cannabinoids and vanilloids are two distinct groups of substances that share some pharmacological targets. Here we report that two cannabinoid type 1 receptor (CB1) agonists, WIN 55212-2 (WIN) and arachidonyl-2'-chloroethylamide (ACEA) have opposing effects on evoked quantal acetylcholine release - WIN decreased quantal content while ACEA increased quantal content. The decrease in quantal content by WIN was blocked by the CB1 antagonist AM 251. The increase in quantal content by ACEA was not blocked by AM 251, indicating it acts through a receptor other than CB1. As ACEA is also an agonist for the vanilloid receptor (TRPV1) we tested the effect of vanilloids on quantal content. Similar to ACEA, the vanilloid agonist capsaicin increased quantal content, and this effect was blocked by capsazepine, a TRPV1 antagonist. Capsazepine also blocked the increase in quantal content by ACEA. Together these data show an inhibitory effect of CB1 activation on evoked acetylcholine release and the first evidence for the presence of a vanilloid receptor at the neuromuscular junction.
Silveira
Priscila Elisa
PE
Departamento de Fisiologia e Biofísica, ICB/UFMG, Av. Antônio Carlos 6627, Belo Horizonte, Minas Gerais 31270-901, Brazil.
Silveira
Naiara Araújo
NA
Morini
Verônica de Cássia
Vde C
Kushmerick
Christopher
C
Naves
Lígia Araujo
LA
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology*; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011892:Rana catesbeiana; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000502:physiology; D050916:TRPV Cation Channels / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000502:physiology
D001095:Arachidonic Acids; D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C119325:arachidonyl-2-chloroethylamide; C103505:AM 251; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C071423:capsazepine; D000109:Acetylcholine; D002211:Capsaicin