Endothelin localizes in the dorsal horn and acts on the spinal neurones: possible involvement of dihydropyridine-sensitive calcium channels and substance P release.

The neural effect of endothelin, a vasoconstrictor peptide from vascular endothelium, was investigated in the in vitro spinal cord preparation of the newborn rat. In addition, an immunohistochemical study of endothelin was performed in the porcine spinal cord. Endothelin produced ventral root depolarization in a dose-dependent manner in the newborn rat spinal cord. Endothelin (5 x 10(-8) M)-induced depolarization was depressed by the dihydropyridine-sensitive Ca2+ channel blocker, nicardipine (10(-7) M), or the substance P antagonist, spantide (5 x 10(-6) M). These results suggest that endothelin may cause substance P release and that dihydropyridine-sensitive Ca2+ channels in the spinal cord may be involved in this process. Furthermore, endothelin-like immunoreactivity was localized in dot- and fibre-like structures and neurones in the dorsal horn of the porcine spinal cord. Therefore, it is suggested that endothelin or endothelin-related peptide(s) have a neuromodulatory function in the spinal cord.