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Time‐dependent blockade of neurogenic plasma extravasation in dura mater by 5‐HT 1B/D agonists and endopeptidase 24.11
Author(s) -
Huang Zhihong,
Byun Barkjang,
Matsubara Toshio,
Moskowitz Michael A.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb12805.x
Subject(s) - extravasation , trigeminal ganglion , chemistry , stimulation , evans blue , endocrinology , neurogenic inflammation , medicine , agonist , capsaicin , dura mater , sumatriptan , substance p , receptor , neuropeptide , anatomy , pathology , biology , neuroscience , sensory system
1 The delayed effects of stimulating the trigeminal ganglion unilaterally in rats and guinea‐pigs were assessed by measuring the leakage of radiolabelled albumin from blood into the dura mater at intervals for up to 120 min after a 5 min stimulation period (5 Hz, 0.6 mA, 5 ms). 2 [ 125 I]‐albumin (50 μCi kg −1 ) was injected i.v. as a tracer 0, 20, 50, 80 or 110 min after stimulation and the animals were killed 10 min later. Extravasation of plasma protein developed for up to 90 min poststimulation. 3 To examine the mechanism underlying delayed plasma protein extravasation, CP‐93,129 (5‐HT 1B receptor agonist, 460 nmol kg −1 ), sumatriptan (5‐HT 1B/D receptor agonist, 24 nmol kg −1 ), or neutral endopeptidase 24.11 (1 nmol kg −1 ) were administered 45 or 75 min after trigeminal stimulation and 5 min before radiolabelled albumin. The extravasation response was reduced at 45 min. CP‐23,129 also blocked extravasation when injected 25 min after capsaicin administration (1 μmol kg −1 ). 4 If the tracer was injected 5 min prior to electrical trigeminal stimulation, endopeptidase 24.11 (1 nmol kg −1 ) given 10 min before stimulation blocked the leakage (as reported previously for CP‐93,129 or sumatriptan). All three compounds blocked the leakage when administered 30 min (but not 60 min) poststimulation in this paradigm. 5 The data support the previously made contention that neuropeptide release from sensory fibres mediates the plasma extravasation response following trigeminal ganglion stimulation, and that release and plasma leakage continue many minutes beyond the stimulation period. Hence, drugs that inhibit neuropeptide release (CP‐93,129, sumatriptan), or enhance breakdown of neuropeptide mediators (endopeptidase 24.11) block the delayed extravasation response. Extravasation developing later than 45 min poststimulation was not neurogenically mediated.