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

Abstract

Objective-This study tests the hypothesis that the transient receptor potential vanilloid subtype 1 (TRPV1)-induced neuropeptide secretion and depressor response are mediated by, at least in part, activation of endoplasmic reticulum (ER)-associated Ca 2+ release receptors, leading to increased cytosolic Ca 2+ in dorsal root ganglion (DRG) neurons.Methods/Results-Bolus injection of capsaicin (CAP, 10 or 50 μg/kg), a selective TRPV1 agonist, into anesthetized male Wistar rats caused dose-dependent decreases in mean arterial pressure (MAP, P<0.05). CAP (50 μg/kg)-induced depressor effects and increases in plasma calcitonin gene-related peptide (CGRP) levels (-29±2 mmHg, 82.2±5.0 pg/ml, respectively) were abolished by a selective TRPV1 antagonist, capsazepine (3 mg/kg CAPZ, -4±1 mmHg, 41.8±4.4 pg/ml, P<0.01), and attenuated by a selective ryanodine receptor (RyR) antagonist, dantrolene (5 mg/kg, -12±1 mmHg, 57.2±2.6 pg/ml, P<0.01), but unaffected by an inhibitor of ER Ca 2+ -ATPase, thapsigargin (50 μg/ kg TG, -30±1 mmHg, 73.8±2.3 pg/ml, P>0.05), or an antagonist of the inositol (1,4,5)-trisphosphate receptor (IP 3 R), 2-aminoethoxydiphenyl borate (3 mg/kg 2-APB, -34±5 mmHg, 69.0±3.7 pg/ml, P>0.05). CGRP (1 mg/kg), a selective CGRP receptor antagonist, also blocked CAP-induced depressor effects. In contrast, dantrolene had no effect on CGRP (1 μg/kg)-induced depressor effects. In vitro, CAP (0.3 μM) increased intracellular Ca 2+ concentrations and CGRP release from freshly isolated sensory neurons in DRG (P<0.01), which were blocked by CAPZ (10 μM) and attenuated by dantrolene but not TG or 2-APB.Conclusion-Our results indicate that TRPV1 activation triggers RyR-but not IP 3 R-dependent Ca 2+ release from ER in DRG neurons leading to increased CGRP release and consequent depressor effects.

Effects of a High-Salt Diet on TRPV-1-Dependent Renal Nerve Activity in Dahl Salt-Sensitive Rats

“…The data in the present study show that TRPV1-induced SP release from the renal pelvis is suppressed in DS, but not in DR or DOCA, rats given HS, indicating that effector function, in addition to afferent function, of TRPV1-positive nerves is impaired in DS rats when loaded with salt and that such impairment in diminished SP release upon TRPV1 activation may underlie observed weakened TRPV1 action in DS rats fed a HS diet. Furthermore, TRPV1-triggered release of CGRP from the renal pelvis is also suppressed in DS rats given a HS diet, indicating that TRPV1-mediated protection against salt-induced hypertension via CGRP release may be disturbed in DS rats challenged with salt loading [30]. …”

Minding the calcium store: Ryanodine receptor activation as a convergent mechanism of PCB toxicity

“…Diverse neurochemical changes associated with dendritic synaptic plasticity have been shown to rely on RyR function, including: 1) activity-dependent postsynaptic translation (Jourdi et al, 2009) and secretion (Kolarow, Brigadski, & Lessmann, 2007) of neurotrophins, 2) modulation of Gq-coupled receptor function by stress peptides and hormones (Riegel & Williams, 2008); 3) activity-dependent enhancement of glutamate responses and the associated increase of GluR1 within spines mediated by synaptopodin, an actin-binding protein that co-localizes with RyRs within the spine apparatus of hippocampal neurons (Vlachos et al, 2009); and 4) sequential activation of CaM kinases, CREB and transcription of genes encoding Ca 2+ -regulated proteins triggered by repetitive or prolonged depolarization of hippocampal neurons (Deisseroth, Heist, & Tsien, 1998). RyRs similarly function in peripheral neurons to regulate the release of (Cong, Takeuchi, Tokuno, & Kuba, 2004; W. Huang, Wang, Galligan, & Wang, 2008; Ouyang et al, 2005) and response to (Brain, Trout, Jackson, Dass, & Cunnane, 2001; Locknar, Barstow, Tompkins, Merriam, & Parsons, 2004) neurotransmitters and neuropeptides, and their function underlies the exocytotic release of glutamate from astrocytes (reviewed in Reyes & Parpura, 2009).…”

Topical herbal therapies for treating osteoarthritis

“…Binding of capsaicin to this target is accompanied by a decrease in membrane resistance, depolarization and activation of synaptosomal neurotransmitter release (Buck&Burks 1986;Huang 2008; Sauer 2001; Zhao 1992). Following the initial activation, which is often associated with heat sensation, desensitation and depletion of neurotransmitters produce the capsaicinoid (expressed as capsaicin) analgesic effect.…”