BACKGROUND: Recent evidences suggest that anesthetic action within the spinal cord is important in suppressing somatic responses to painful stimuli. Intrathecal endothelin-1 (ET-1) is known to have antinociceptive effect. The purpose of this experiment was to determine whether intrathecal ET-1 may influence the minimum alveolar concentration (MAC) of isoflurane in rats and access the role of the spinal cord as the sites of anesthetic action in blocking somatic responsiveness. METHODS: In Sprague-Dawley rats fitted with an indwelling intrathecal catheter, we determined the MAC of isoflurane using a tail-clamp technique as a painful stimulus, combined with end-tidal anesthetic sampling. In experiment 1, the control MAC was determined and changes of control MAC were observed after intrathecal ET-1 (4x10-2 nmol, 4x10-3 nmol) administration. In experiment 2, we observed the effects of L or N type Ca++ channel blocker such as verapamil (50 g) or W-conotoxin (0.5 g) on the MAC after measurement of the control MAC. In experiment 3, after measurement of the control MAC, ET-1 (10-2 nmol) was administered intrathecally and the MAC was determined again. Next, intrathecal verapamil (50 g) or W-conotoxin (0.5 g) was injected. After that, the MAC was determined again. RESULTS: In experiment 1, ET-1 decreased the MAC of isoflurane and its effect was sustained over 2 hours. In experiment 2, the MAC, determined following administration of verapamil or W-conotoxin, was not different from that of the control. In experiment 3, the MAC was decreased after ET-1 administration and then increased following injection of verapamil or W-conotoxin. CONCLUSIONS: These results suggested that ET-1, in relation to calcium, might play an important role in determining the MAC of isoflurane in the spinal cord.