alpha-eudesmol, a P/Q-type Ca(2+) channel blocker, inhibits neurogenic vasodilation and extravasation following electrical stimulation of trigeminal ganglion.

Abstract

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.

• Authors: K Asakura, T Kanemasa, K Minagawa, K Kagawa, T Yagami, M Nakajima, M Ninomiya
• Journal: Brain research (Brain Res) Vol. 873 Issue 1 Pg. 94-101 (Aug 04 2000) ISSN: 0006-8993 [Print] Netherlands
• PMID: 10915814 (Publication Type: Journal Article)

Chemical References

• Calcium Channel Blockers
• Calcium Channels, P-Type
• Calcium Channels, Q-Type
• Sesquiterpenes, Eudesmane
• Terpenes
• Substance P
• Evans Blue
• alpha-eudesmol
• Calcitonin Gene-Related Peptide

Topics

• Animals
• Blood Pressure (drug effects)
• Calcitonin Gene-Related Peptide (metabolism)
• Calcium Channel Blockers (pharmacology)
• Calcium Channels, P-Type (drug effects)
• Calcium Channels, Q-Type (drug effects)
• Electric Stimulation
• Evans Blue (pharmacokinetics)
• Extravasation of Diagnostic and Therapeutic Materials (metabolism)
• Face
• Nerve Endings (metabolism)
• Neurons, Afferent (metabolism)
• Rats
• Rats, Wistar
• Sesquiterpenes, Eudesmane
• Skin (blood supply)
• Spinal Cord (cytology, metabolism)
• Substance P (metabolism)
• Terpenes (pharmacology)
• Trigeminal Ganglion (physiology)
• Vasodilation (drug effects, physiology)