Abnormal response to ryanodine in oesophageal striated muscle of spontaneously hypertensive rats

Sekiguchi, Fumiko; Kawata, Kyoko; Yamazoe, Masako; Sunano, Satoru

doi:10.1016/j.ejphar.2003.11.081

Cited by 1 publication

(1 citation statement)

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“…Although the mechanisms responsible for such defects remain to be elucidated, recent studies showed that RyR function in various tissues including the heart and oesophageal striated muscle is impaired in experimental hypertensive rats or SHR 49-50. Given the fact that RyR may play an important role in TRPV1-mediated CGRP release and hypotension, it is conceivable that dysfunction of RyR may contribute to impaired action mediated by TRPV1 and TRPV1-positive sensory nerves in hypertension, and that agents that modulate the RyR function may be beneficial in improving sensory nerve function and in treating hypertension.…”

Section: Perspectivesmentioning

confidence: 99%

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

Wang

Galligan

et al. 2008

Journal of Hypertension

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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.

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Section: Perspectivesmentioning

confidence: 99%