Cannabinoid inhibition of capsaicin-sensitive sensory neurotransmission inthe rat mesenteric arterial bed

The present study investigated whether cannabinoids can modulate neurotrans mission mediated by capsaicin-sensitive sensory nerves in the rat isolated mesenteric arterial bed. Sensory neurogenic vasorelaxation mediated by elec trical field stimulation was concentration-dependently attenuated by HU210 (0.1-3 muM), a cannabinoid receptor agonist (from 62 +/- 8.3% to 6 +/- 2.1% at 3 muM HU210) I-fil210 had no effect on relaxation to exogenous calciton in gene-related peptide, indicating a prejunctional action. The action of H U210(I muM) was not affected by LY320135 (1 muM) or SR144528 (1 muM). canna binoid CB1 and CB2 receptor antagonists, respectively. SR141716A (0.01-1 mu M), a cannabinoid CB1 receptor antagonist, concentration-dependently augmen ted vasorelaxation to electrical field stimulation, but had no effect on re sponses to calcitonin gene-related peptide and capsaicin, indicating a poss ible role of endogenous cannabinoids in sensory neurotransmission in rat me senteric arteries. These data show that the cannabinoid receptor agonist HU 210 inhibits prejunctionally sensory neurotransmission in rat mesenteric ar teries and that this action is independent of cannabinoid CB1- or CB2-like receptors. (C) 2001 Elsevier Science B.V. All rights reserved.