Inhibitory effects of cannabinoid receptor ligands on electrically-evoked responses in rat isolated tracheal ring segments

We have examined the possible existence of cannabinoid receptors in the iso lated rat tracheal ring segments by studying the effects of some cannabinoi d receptor ligands on electrically-induced contractions. Anandamide (10(-8) -3 x 10(-5) M), an endogenous ligand for cannabinoid receptors, and WIN 55, 212-2 (10(-9)-3 x 10(-5) M), a moderately selective CB2 agonist, inhibited electrically evoked contractions of the rat tracheal ring segments in a con centration-related manner. Addition of phentolamine (10(-6) M) to Krebs Hen seleit solution to block alpha(2)-adrenoceptors did not affect anandamide-i nduced inhibition of the electrically evoked contractions. The EC25 (-log M ) values were 5.25 +/- 0.2 and 5.8 +/- 0.4 for anandamide and WIN 55,212-2, respectively. The maximal inhibition produced by the highest concentration of the agonists used was 51.4 +/- 5.8% for anandamide and 35.1 +/- 19.5% f or WIN 55,212-2. WIN 55,212-3 also produced a concentration-dependent inhib ition of the electrically evoked contractions. The maximal inhibition produ ced by WIN 55,212-3 was 15.8 +/- 2.4. The inhibitory effects of anandamide and WIN 55,212-2 were not attenuated by SR141716A (10(-6) M), a selective C B1 receptor antagonist. Anandamide (10(-8)-3 x 10(-5) M) did not relax rat tracheal, ring segments pre-contracted with carbachol (10(-6) M). These res ults suggest that anandamide and WIN 55,212-2 produce pre-junctional inhibi tory effects in the rat trachea and that these effects were likely mediated through cannabinoid CB2 receptors. These effects were probably non-cannabi noid receptor-mediated considering the high concentrations of the agents re quired to produce inhibitory responses and the effectiveness of WIN 55,212- 3. (C) 1999 Academic Press.