Dihydroergotamine and sumatriptan attenuate levels of CGRP in plasma in rat superior sagittal sinus during electrical stimulation of the trigeminal ganglion

M. Gabriella Buzzi, W. B. Carter, T. Shimizu, H. Heath, M. A. Moskowitz

Research output: Contribution to journalArticle

Abstract

Vasoactive neuropeptides, present in unmyelinated C-fibers, can be released from perivascular sensory axons by antidromic stimulation, to mediate vasodilation and extravasation of plasma protein (neurogenic inflammation). In this report, the effects of antidromic trigeminal stimulation on levels of calcitonin gene-related peptide (CGRP) in plasma were examined in the superior sagittal sinus and the effects of drugs that have been shown previously to block extravasation of neurogenic plasma determined. The levels of immunoreactive CGRP in plasma were measured both before and during electrical stimulation of the trigeminal ganglion (0.1-1.0 mA, 5 msec, 5 Hz, 3-5 min), using a highly specific and sensitive immunochemiluminometric assay. Levels of CGRP increased and became maximal within the first minute of stimulation. The increases were detectable at intensities of current as small as 0.1 mA. Peak levels related to the intensity of the stimulus. Samples from femoral arterial blood did not show concomitant increases at 1 min. Pretreatment with dihydroergotamine (DHE) (50 μg/kg i.v.) did not change the baseline levels but decreased levels of CGRP during stimulation (0.3 mA), by 55% at 1 min and 50% at 3 min. Sumatriptan (GR43175) (300 μg/kg) attenuated the increase by 57% at 3 min (0.1 mA, 5 msec, 5 Hz) but not after 1 min of stimulation, although decreases were observed at the latter time during an individual experiment. Drug-induced attenuation of levels of CGRP in plasma may reflect inhibition of release, to thereby provide evidence to explain blockade of neurogenic extravasation of plasma.

Original languageEnglish
Pages (from-to)1193-1200
Number of pages8
JournalNeuropharmacology
Volume30
Issue number11
DOIs
Publication statusPublished - 1991

Fingerprint

Dihydroergotamine
Superior Sagittal Sinus
Sumatriptan
Trigeminal Ganglion
Calcitonin Gene-Related Peptide
Electric Stimulation
Neurogenic Inflammation
Unmyelinated Nerve Fibers
Thigh
Neuropeptides
Vasodilation
Pharmaceutical Preparations
Axons
Blood Proteins

Keywords

  • 5-HT
  • calcitonin gene-related peptide
  • migraine
  • neurogenic inflammation
  • prejunctional receptors

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Dihydroergotamine and sumatriptan attenuate levels of CGRP in plasma in rat superior sagittal sinus during electrical stimulation of the trigeminal ganglion. / Buzzi, M. Gabriella; Carter, W. B.; Shimizu, T.; Heath, H.; Moskowitz, M. A.

In: Neuropharmacology, Vol. 30, No. 11, 1991, p. 1193-1200.

Research output: Contribution to journalArticle

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abstract = "Vasoactive neuropeptides, present in unmyelinated C-fibers, can be released from perivascular sensory axons by antidromic stimulation, to mediate vasodilation and extravasation of plasma protein (neurogenic inflammation). In this report, the effects of antidromic trigeminal stimulation on levels of calcitonin gene-related peptide (CGRP) in plasma were examined in the superior sagittal sinus and the effects of drugs that have been shown previously to block extravasation of neurogenic plasma determined. The levels of immunoreactive CGRP in plasma were measured both before and during electrical stimulation of the trigeminal ganglion (0.1-1.0 mA, 5 msec, 5 Hz, 3-5 min), using a highly specific and sensitive immunochemiluminometric assay. Levels of CGRP increased and became maximal within the first minute of stimulation. The increases were detectable at intensities of current as small as 0.1 mA. Peak levels related to the intensity of the stimulus. Samples from femoral arterial blood did not show concomitant increases at 1 min. Pretreatment with dihydroergotamine (DHE) (50 μg/kg i.v.) did not change the baseline levels but decreased levels of CGRP during stimulation (0.3 mA), by 55{\%} at 1 min and 50{\%} at 3 min. Sumatriptan (GR43175) (300 μg/kg) attenuated the increase by 57{\%} at 3 min (0.1 mA, 5 msec, 5 Hz) but not after 1 min of stimulation, although decreases were observed at the latter time during an individual experiment. Drug-induced attenuation of levels of CGRP in plasma may reflect inhibition of release, to thereby provide evidence to explain blockade of neurogenic extravasation of plasma.",
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