Institutional members access full text with Ovid®

Share this article on:

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

doi: 10.1097/HJH.0b013e328309eff9
Original papers: Pathophysiological aspects

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.

aDepartment of Medicine and Pharmacology & Toxicology, Michigan State University, East Lansing, Michigan, USA

bDepartment of Cardiology of the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

Received 21 January, 2008

Revised 24 April, 2008

Accepted 23 May, 2008

Correspondence to Donna H. Wang, MD, Department of Medicine, B316 Clinical Center, Michigan State University, East Lansing, MI 48824, USA E-mail: Donna.Wang@ht.msu.edu

© 2008 Lippincott Williams & Wilkins, Inc.