ANANDAMIDE, A NATURALLY-OCCURRING AGONIST OF THE CANNABINOID RECEPTOR, BLOCKS ADENYLATE-CYCLASE AT THE FROG NEUROMUSCULAR-JUNCTION

Anandamide (arachydonylethanolamide) is a naturally-occurring ligand o f the cannabinoid receptor. When anandamide binds to its receptor, ade nylate cyclase is inhibited. At the frog neuromuscular junction, anand amide lessened the increase in quantal size produced by pretreatment i n hypertonic solution. It did not alter the increases in quantal size produced by insulin or by a permeable agonist of cAMP. It was known th at hypertonic treatment increases quantal size by way of the cAMP-prot ein kinase A pathway. Anandamide had no effect on miniature endplate p otential frequency (f(mepp)) in untreated preparations. After f(mepp) was increased in the presence of a permeable cAMP agonist, anandamide brought f(mepp) back to resting levels. The conclusions are that the m otor nerve terminal has a cannabinoid receptor. The binding of anandam ide to this receptor seems to block adenylate cyclase.