Intracerebroventricular endothelin-1 (ET-1) produces Ca(2+)-mediated antinociception in mice.

Intracerebroventricular (i.c.v.) administration of endothelin-1 (ET-1) at doses of 0.313, 0.625, 1.25, 2.5 and 5 pmol/mouse produced a strong antinociceptive effect as evaluated by hot plate method in mice. The effect was dose-dependent and lasted for more than 120 min. The opioid receptor antagonist naloxone did not antagonize, and the cyclooxygenase inhibitors indomethacin and diclofenac slightly inhibited the ET-1 effect. The calcium overload blocker cinnarizine antagonized the antinociceptive effect of ET-1, suggesting that the ET-1 effect might be Ca(2+)-mediated.