Yohimbine inhibits firing activities of rat dorsal root ganglion neurons by blocking Na+ channels and vanilloid VR1 receptors.
Yohimbine, an indole alkaloid, is a natural alpha(2)-adrenoceptor antagonist and is frequently used to assess the mechanism of a drug's effect on alpha-adrenoceptors. Recently, several studies showed that yohimbine exhibited analgesic effects in in vivo animal models. However, the underlying mechanism is not known. We investigated the effects of yohimbine on Na(+) channels and vanilloid VR1 receptors in dorsal root ganglion cells. We found that yohimbine inhibited tetrodotoxin-sensitive Na(+) channels (Na(V)1.2), the tetrodotoxin-resistant Na(+) channels, including both slow inactivating (Na(V)1.8) and persistent (Na(V)1.9) Na(+) channels, and capsaicin-sensitive vanilloid VR1 receptors. Action potential firing activities of dorsal root ganglion neurons evoked by current injection or capsaicin were eliminated by yohimbine. The blocking effects of yohimbine on nociceptive-related ion channels and firing activities of dorsal root ganglion neurons may underlie the ionic mechanism of yohimbine's analgesic effects observed in in vivo studies.
Dessaint
John
J
Department of Electrophysiology, Neurogen Corporation, 35 Northeast Industrial Road, Branford, CT 06405, USA.
Yu
Weifeng
W
Krause
James E
JE
Yue
Lixia
L
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000037:antagonists & inhibitors* / Q000502:physiology; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology*
D011955:Receptors, Drug; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D015016:Yohimbine