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.
Dymshitz
J
J
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202-5120.
Vasko
M R
MR
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D016232:Endothelins / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism*
D016232:Endothelins; D013373:Substance P; D006152:Cyclic GMP; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin