Endothelin-1 enhances capsaicin-induced peptide release and cGMP accumulation in cultures of rat sensory neurons.

Because endothelin-1 (ET-1) may be a neuromodulator in sensory systems, we examined whether this peptide could alter release of substance P (SP) and calcitonin gene-related peptide (CGRP) from isolated sensory neurons. Although ET-1 had minimal actions on spontaneous neuropeptide release, pretreating cultures with 500 nM resulted in a 50% augmentation of SP and CGRP release evoked by 50 nM capsaicin. Moreover, 2000 nM ET-1 enhanced capsaicin-evoked release of CGRP two fold. In an analogous manner, ET-1 alone did not alter intracellular cGMP content, but enhanced the increase in cGMP caused by 50 nM capsaicin. Intracellular cAMP was not altered by capsaicin and/or ET-1. These data suggest that ET-1 may play a role in modulation of peptide release from primary afferent neurons.