Journal of Hypertension

Skip Navigation LinksHome > October 2008 - Volume 26 - Issue 10 > Transient receptor potential vanilloid subtype 1 channel med...
Journal of Hypertension:
doi: 10.1097/HJH.0b013e328309eff9
Original papers: Pathophysiological aspects

Transient receptor potential vanilloid subtype 1 channel mediated neuropeptide secretion and depressor effects: role of endoplasmic reticulum associated Ca2+ release receptors in rat dorsal root ganglion neurons

Huang, Weia,b; Wang, Huia; Galligan, James Ja; Wang, Donna Ha

Collapse Box

Abstract

Objective: This study tests the hypothesis that the transient receptor potential vanilloid subtype 1 channel induced neuropeptide secretion and depressor response are mediated by, at least in part, activation of endoplasmic reticulum associated Ca2+ release receptors, leading to increased cytosolic Ca2+ in dorsal root ganglion neurons.

Methods/results: Bolus injection of capsaicin (10 or 50 μg/kg), a selective transient receptor potential vanilloid subtype 1 channel agonist, into anesthetized male Wistar rats caused a dose-dependent decrease in mean arterial pressure (P < 0.05). Capsaicin (50 μg/kg)-induced depressor effects and increase in plasma calcitonin gene related peptide (CGRP) levels (−29 ± 2 mmHg, 82.2 ± 5.0 pg/ml) were abolished by a selective transient receptor potential vanilloid subtype 1 channel antagonist, capsazepine (3 mg/kg, −4 ± 1 mmHg, 41.8 ± 4.4 pg/ml, P < 0.01), and attenuated by a selective ryanodine receptor antagonist, dantrolene (5 mg/kg, −12 ± 1 mmHg, 57.2 ± 2.6 pg/ml, P < 0.01), but unaffected by an inhibitor of endoplasmic reticulum Ca2+-ATPase, thapsigargin (50 μg/kg, −30 ± 1 mmHg, 73.8 ± 2.3 pg/ml, P > 0.05), or an antagonist of the inositol (1,4,5)-trisphosphate receptor, 2-aminoethoxydiphenyl borate (3 mg/kg, −34 ± 5 mmHg, 69.0 ± 3.7 pg/ml, P > 0.05). CGRP8–37 (1 mg/kg), a selective CGRP receptor antagonist, also blocked capsaicin-induced depressor effects. In contrast, dantrolene had no effect on CGRP (1 μg/kg)-induced depressor effects. In vitro, capsaicin (0.3 μmol/l) increased intracellular Ca2+ concentrations and CGRP release from freshly isolated sensory neurons in dorsal root ganglion (P < 0.01), which were blocked by capsazepine (10 μmol/l) and attenuated by dantrolene but not thapsigargin or 2-aminoethoxydiphenyl borate.

Conclusion: Our results indicate that transient receptor potential vanilloid subtype 1 channel activation triggers ryanodine receptor but not inositol (1,4,5)-trisphosphate receptor dependent Ca2+ release from endoplasmic reticulum in dorsal root ganglion neurons, leading to increased CGRP release and consequent depressor effects.

© 2008 Lippincott Williams & Wilkins, Inc.

Login

Article Tools

Share

Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.