Differential regulation of TRPV1 channels by H2O2: implications for diabetic microvascular dysfunction.
*Coronary Circulation; *Microcirculation; Animals; Capsaicin; Coronary blood flow; Diabetic Angiopathies/*metabolism; HEK293 Cells; Humans; Hydrogen peroxide; Hydrogen Peroxide/*metabolism; Inbred C57BL; Knockout; Male; Mice; Reactive oxygen species; TRPV Cation Channels/*metabolism; TRPV1
We demonstrated previously that TRPV1-dependent coupling of coronary blood flow (CBF) to metabolism is disrupted in diabetes. A critical amount of H2O2 contributes to CBF regulation; however, excessive H2O2 impairs responses. We sought to determine the extent to which differential regulation of TRPV1 by H2O2 modulates CBF and vascular reactivity in diabetes. We used contrast echocardiography to study TRPV1 knockout (V1KO), db/db diabetic, and wild type C57BKS/J (WT) mice. H2O2 dose-dependently increased CBF in WT mice, a response blocked by the TRPV1 antagonist SB366791. H2O2-induced vasodilation was significantly inhibited in db/db and V1KO mice. H2O2 caused robust
DelloStritto Daniel J; Connell Patrick J; Dick Gregory M; Fancher Ibra S; Klarich Brittany; Fahmy Joseph N; Kang Patrick T; Chen Yeong-Renn; Damron Derek S; Thodeti Charles K; Bratz Ian N
Basic research in cardiology
2016
2016-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00395-016-0539-4" target="_blank" rel="noreferrer noopener">10.1007/s00395-016-0539-4</a>
Propofol restores transient receptor potential vanilloid receptor subtype-1 sensitivity via activation of transient receptor potential ankyrin receptor subtype-1 in sensory neurons.
Male; Mice; Capsaicin; Cells; Anesthetics; Animal Studies; Genes – Drug Effects; Carrier Proteins – Drug Effects; Carrier Proteins – Metabolism; Intravenous – Pharmacodynamics; Propofol – Pharmacodynamics; Sensory Receptor Cells – Drug Effects
Background: Cross talk between peripheral nociceptors belonging to the transient receptor potential vanilloid receptor subtype-1 (TRPV1) and ankyrin subtype-1 (TRPA1) family has been demonstrated recently. Moreover, the intravenous anesthetic propofol has directly activates TRPA1 receptors and indirectly restores sensitivity of TRPV1 receptors in dorsal root ganglion (DRG) sensory neurons. Our objective was to determine the extent to which TRPA1 activation is involved in mediating the propofol-induced restoration of TRPV1 sensitivity.Methods: Mouse DRG neurons were isolated by enzymatic dissociation and grown for 24 h. F-11 cells were transfected with complementary DNA for both TRPV1 and TRPA1 or TRPV1 only. The intracellular Ca concentration was measured in individual cells via fluorescence microscopy. After TRPV1 desensitization with capsaicin (100 nM), cells were treated with propofol (1, 5, and 10 μM) alone or with propofol in the presence of the TRPA1 antagonist, HC-030031 (0.5 μM), or the TRPA1 agonist, allyl isothiocyanate (AITC; 100 μM); capsaicin was then reapplied.Results: In DRG neurons that contain both TRPV1 and TRPA1, propofol and AITC restored TRPV1 sensitivity. However, in DRG neurons containing only TRPV1 receptors, exposure to propofol or AITC after desensitization did not restore capsaicin-induced TRPV1 sensitivity. Similarly, in F-11 cells transfected with both TRPV1 and TRPA1, propofol and AITC restored TRPV1 sensitivity. However, in F-11 cells transfected with TRPV1 only, neither propofol nor AITC was capable of restoring TRPV1 sensitivity.Conclusions: These data demonstrate that propofol restores TRPV1 sensitivity in primary DRG neurons and in cultured F-11 cells transfected with both the TRPV1 and TRPA1 receptors via a TRPA1-dependent process. Propofol's effects on sensory neurons may be clinically important and may contribute to peripheral sensitization to nociceptive stimuli in traumatized tissue.
Zhang H; Wickley PJ; Sinha S; Bratz IN; Damron DS; Zhang Hongyu; Wickley Peter J; Sinha Sayantani; Bratz Ian N; Damron Derek S
Anesthesiology
2011
2011-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1097/ALN.0b013e31820dee67" target="_blank" rel="noreferrer noopener">10.1097/ALN.0b013e31820dee67</a>
Oropharyngeal capsaicin exposure improves infant feeding performance in an animal model of superior laryngeal nerve damage
Sensorimotor feedback is critical to safe and effective swallowing. Because of this, sensory interventions have the potential to treat dysphagia. One such treatment may be found in capsaicin, which activates the internal branch of the superior laryngeal nerve (iSLN). The iSLN initiates the pharyngeal swallow, and a more sensitive iSLN should more readily elicit swallowing and improve swallow safety. We explored the neurophysiological mechanism by which capsaicin improves swallow performance using an infant pig model with a unilateral iSLN lesion. Using high-speed videofluoroscopy, we collected oropharyngeal kinematic data while pigs suckled on bottles, before and after applying capsaicin to the posterior tongue and valleculae. We found that capsaicin application decreased maximal bolus sizes, which improved swallow safety. Furthermore, capsaicin improved performance when infant pigs swallowed more moderately sized boluses. However, capsaicin did not change swallow frequency, the number of sucks prior to each swallow, nor total pharyngeal transit time (TPT). Similarly, excursions of the hyoid, thyroid, and posterior tongue were unchanged. TPT and hyoid and thyroid excursions maintained relationships with bolus size post-capsaicin, suggesting that these variables are less sensitive to sensory intervention. The timing and extent of posterior tongue movement were only correlated with bolus size pre-capsaicin, which could imply that capsaicin fundamentally changes in relationships between tongue movements and bolus size. Our results provide insight into the neural control of swallowing and capsaicin's mechanism of action, and suggest that capsaicin may be beneficial in treating acute infant dysphagia. NEW & NOTEWORTHY Chemical sensory interventions alter swallow physiology, which is well-documented in adults but relatively unexplored in infants. Using videofluoroscopy, we found that capsaicin exposure limited infant pigs' bolus sizes to improve swallow performance without changing swallow frequency. Capsaicin increased the likelihood of safe swallowing with more moderately sized boluses and changed relationships between bolus size and tongue movements, which may impact performance. This work highlights the potential role of capsaicin in treating acute infant dysphagia.
Chloe E Edmonds
Rebecca Z German
Laura E Bond
Christopher J Mayerl
J Neurophysiol
. 2022 Aug 1;128(2):339-349. doi: 10.1152/jn.00063.2022. Epub 2022 Jul 13.
2022
English