TRPV1 activation results in disruption of the blood-brain barrier in the rat

D E Hu, A S Easton, P A Fraser

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48 Citations (Scopus)

Abstract

1 We have examined the role of TRPV1 activation in disrupting the blood-brain barrier by measuring the permeability of single pial venular capillaries in anaesthetized rats. 2 Capsaicin application to the brain surface resulted in increased permeability, maximal 2.1 +/- 0.12 x 10(-6) cm s(-1) (mean +/- s.e.m.) with log EC50 -4.5 +/- 0.10. Substance P methyl ester gave a similar response (maximal 2.0 +/- 0.07, n=6, log EC50 -4.8 +/- 0.07), but the selective NK2 agonist, beta-Ala(8)-NKA(4-10) peptide, had no effect. Although CGRP decreased the permeability of venules (log EC50 10.3 +/- 0.11), its receptor antagonist CGRP(8-37) had no effect on the response to capsaicin. 3 The TRPV1 antagonist capsazepine (I mm) reduced the response to capsaicin (100 mu M), from 1.78 +/- 0.15 to 0.63 +/- 0.10 (n=4). The NK1 receptor antagonists GR205171 (100 mu M) and SDZ NKT 376 (1 mm) also reduced the response to capsaicin (from 1.75 +/- 0.14 to 0.46 +/- 0.08; n=6, and from 1.85 +/- 0.13 to 0.48 +/- 0.05; n=5, respectively), indicating that capsaicin acts via TRPV1 in series with NK1. 4 Starch microspheres were used to produce transient focal ischaemia. Permeability was increased on reperfusion to a greater extent and more rapidly in vessels with diameter greater than 40 mu m than those less than 15 mu m. Capsazepine given intraperitoneally during ischaemia reduced the permeability increase in small venules from 5.9 +/- 0.3 to 2.4 +/- 0. 1, and from 11.4 +/- 0.8 to 5.1 +/- 0.9 in large venules. 5 In conclusion, the TRPV1 receptor is active in the brain microvasculature and has its permeability-increasing effect via substance P. It also plays a role in the immediate blood-brain barrier disruption following ischaemia-reperfusion
Original languageEnglish
Pages (from-to)576 - 584
Number of pages9
JournalBritish Journal of Pharmacology
Volume146
Issue number4
DOIs
Publication statusPublished - Oct 2005

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