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NEUROPHARMACOLOGY

Effects of Cannabinoids on Synaptic Transmission in the Frog Neuromuscular Junction

Unidad de Investigacion Enrico Stefani del Centro Universitario de Investigaciones Biomedicas, Universidad de Colima, Colima, Mexico

This study aimed to investigate the function of the cannabinoid receptor in the neuromuscular junction of the frog (Rana pipiens). Miniature end-plate potentials were recorded using the intracellular electrode recording technique in the cutaneous pectoris muscle in the presence of the cannabinoid agonists WIN55212-2 (WIN; R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)]-pyrolol[1,2,3de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone) and arachidonylcyclopropylamide [ACPA; N-(2-cyclopropyl)-5Z,8Z,11Z,147-eicosatetraenamide] and the cannabinoid antagonists 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide (AM281) and 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone (AM630). Adding WIN to the external medium decreased the frequency and amplitude of the miniature end-plate potentials (MEPPs); the WIN EC₅₀ value was 5.8 ± 1.0 µM. Application of ACPA, a selective agonist of cannabinoid receptor CB₁, also decreased the frequency of the MEPPs; the ACPA EC₅₀ value was 115.5 ± 6.5 nM. The CB₂ antagonist AM630 did not inhibit the effects of WIN, indicating that its action is not mediated through the CB₂ receptor. However, the CB₁ antagonist AM281 inhibited the effects of WIN and ACPA, suggesting that their actions are mediated through the CB₁ receptor. Pretreatment with the pertussis toxin inhibited the effects of WIN and ACPA, suggesting that their effects are mediated through G_i/o protein activation. The N-type Ca²⁺ channel blocker -conotoxin GVIA (-CgTX) diminished the frequency of the MEPPs, with an -CgTX EC₅₀ value of 2.5 ± 0.40 µM. Blocking the N-type Ca²⁺ channels with 5 µM -CgTX before addition of ACPA to the bath had no additional inhibitory effect on the MEPPs, whereas in the presence of 1 µM -CgTX, ACPA had an additional inhibition effect. These results suggest that cannabinoids modulate transmitter release in the end-plate of the frog neuromuscular junction by activating CB₁ cannabinoid receptors in the nerve ending.

Address correspondence to: Dr. Miguel Huerta, Universidad de Colima, Centro Universitario de Investigaciones Biomédicas, Av. 25 de Julio #965, Colonia Villa San Sebastián, Apartado Postal 11, C.P. 28000-Colima, Colima, México. E-mail: huertam{at}cgic.ucol.mx