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TRPV1 activation results in disruption of the blood-brain barrier in the rat.
Hu, De-En; Easton, Alexander S; Fraser, Paul A.
Afiliação
  • Hu DE; King's College London, Cardiovascular Division, New Hunt's House, Guy's Campus, London SE1 1UL.
Br J Pharmacol ; 146(4): 576-84, 2005 Oct.
Article em En | MEDLINE | ID: mdl-16056236
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. 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-Ala8-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. The TRPV1 antagonist capsazepine (1 mM) reduced the response to capsaicin (100 microM), from 1.78+/-0.15 to 0.63+/-0.10 (n = 4). The NK1 receptor antagonists GR205171 (100 microM) 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 NK(1). 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 microm than those less than 15 microm. 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. 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Capilares / Permeabilidade Capilar / Barreira Hematoencefálica / Canais de Cátion TRPV Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Br J Pharmacol Ano de publicação: 2005 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Capilares / Permeabilidade Capilar / Barreira Hematoencefálica / Canais de Cátion TRPV Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Br J Pharmacol Ano de publicação: 2005 Tipo de documento: Article