alpha-eudesmol, a P/Q-type Ca(2+) channel blocker, inhibits neurogenic vasodilation and extravasation following electrical stimulation of trigeminal ganglion.
In this study, we investigated the effect of alpha-eudesmol, which potently inhibits the presynaptic omega-agatoxin IVA-sensitive (P/Q-type) Ca(2+) channel, on neurogenic inflammation following electrical stimulation of rat trigeminal ganglion. Treatment with alpha-eudesmol (0.1-1 mg/kg. i.v.) dose-dependently attenuated neurogenic vasodilation in facial skin monitored by a laser Doppler flowmetry. In addition, alpha-eudesmol (1 mg/kg. i.v.) significantly decreased dural plasma extravasation in analysis using Evans blue as a plasma marker. On the other hand, alpha-eudesmol (1 mg/kg, i.v.) did not affect mean arterial blood pressure in rats. The calcitonin gene-related peptide (CGRP) and substance P (SP) released from activated sensory nerves have recently been suggested to be associated with the neurogenic inflammation. In this study, we also showed that alpha-eudesmol (0.45-45 microM) concentration-dependently inhibits the depolarization-evoked CGRP and SP release from sensory nerve terminals in spinal cord slices. These results indicate that the anti-neurogenic inflammation action of alpha-eudesmol, which does not affect the cardiovascular system, may be due to its presynaptic inhibition of the neuropeptide release from perivascular trigeminal terminals. We also suggest that the omega-agatoxin IVA-sensitive Ca(2+) channel blocker, alpha-eudesmol, may become useful for the treatment of the neurogenic inflammation in the trigemino-vascular system such as migraine.
Discovery Research Laboratories, Shionogi & Co., Ltd., Toyonaka, Osaka, Japan.
K
K
Asakura
T
T
Kanemasa
K
K
Minagawa
K
K
Kagawa
T
T
Yagami
M
M
Nakajima
M
M
Ninomiya
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020865:Calcium Channels, P-Type / Q000187:drug effects; D020907:Calcium Channels, Q-Type / Q000187:drug effects; D004558:Electric Stimulation; D005070:Evans Blue / Q000493:pharmacokinetics; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000378:metabolism*; D005145:Face; D009411:Nerve Endings / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D045787:Sesquiterpenes, Eudesmane; D012867:Skin / Q000098:blood supply; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology*; D012668:Trigeminal Ganglion / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D045787:Sesquiterpenes, Eudesmane; D013729:Terpenes; D013373:Substance P; D005070:Evans Blue; C118684:alpha-eudesmol; D015740:Calcitonin Gene-Related Peptide