Skip to main content

Advertisement

SpringerLink
Log in

Endothelin-1 Decreases Excitability of the Dorsal Root Ganglion Neurons via ETB Receptor

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Endothelin-1 (ET-1) has been demonstrated to be a pro-nociceptive as well as an anti-nociceptive agent. However, underlying molecular mechanisms for these pain modulatory actions remain unclear. In the present study, we evaluated the ability of ET-1 to alter the nociceptor excitability using a patch clamp technique in acutely dissociated rat dorsal root ganglion (DRG) neurons. ET-1 produced an increase in threshold current to evoke an action potential (I threshold) and hyperpolarization of resting membrane potential (RMP) indicating decreased excitability of DRG neurons. I threshold increased from 0.25 ± 0.08 to 0.33 ± 0.07 nA and hyperpolarized RMP from −57.51 ± 1.70 to −67.41 ± 2.92 mV by ET-1 (100 nM). The hyperpolarizing effect of ET-1 appears to be orchestrated via modulation of membrane conductances, namely voltage-gated sodium current (I Na) and outward transient potassium current (I KT). ET-1, 30 and 100 nM, decreased the peak I Na by 41.3 ± 6.8 and 74 ± 15.2%, respectively. Additionally, ET-1 (100 nM) significantly potentiated the transient component (I KT) of the potassium currents. ET-1-induced effects were largely attenuated by BQ-788, a selective ETBR blocker. However, a selective ETAR blocker BQ-123 did not alter the effects of ET-1. A selective ETBR agonist, IRL-1620, mimicked the effect of ET-1 on I Na in a concentration-dependent manner (IC50 159.5 ± 92.6 μM). In conclusion, our results demonstrate that ET-1 hyperpolarizes nociceptors by blocking I Na and potentiating I KT through selective activation of ETBR, which may represent one of the underlying mechanisms for reported anti-nociceptive effects of ET-1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

AP:

Action potential

4-AP:

4-Amino pyridine

APD:

Action potential duration

G:

Conductance

τ dec :

Decay phase time constant

I KD :

Delayed rectifier potassium current

DRG:

Dorsal root ganglion

ET-1:

Endothelin-1

ETAR:

Endothelin A receptor

ETBR:

Endothelin B receptor

I KT :

Fast transient potassium currents

G max :

Maximum conductance

PBS:

Phosphate buffer saline

K+ :

Potassium

RMP:

Resting membrane potential

R s :

Series resistance

I Na :

Sodium currents

SEM:

Standard error of mean

TEA:

Tetraethyl ammonium chloride

TTP:

Time to peak

V Na :

Sodium current reversal potential

References

  1. Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K et al (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332(6163):411–415

    Article  CAS  PubMed  Google Scholar 

  2. Khodorova A, Montmayeur JP, Strichartz G (2009) Endothelin receptors and pain. J Pain 10(1):4–28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ferreira SH, Romitelli M, De Nucci G (1989) Endothelin-1 participation in overt and inflammatory pain. J Cardiovasc Pharmacol 13(5):S220–S222

    Article  CAS  PubMed  Google Scholar 

  4. Gokin AP, Fareed MU, Pan HL, Hans G, Strichartz GR, Davar G (2001) Local injection of endothelin-1 produces pain-like behavior and excitation of nociceptors in rats. J Neurosci 21(14):5358

    CAS  PubMed  Google Scholar 

  5. Piovezan AP, D'Orléans-Juste P, Souza GEP, Rae GA (2000) Endothelin-1-induced ETA receptor-mediated nociception, hyperalgesia and oedema in the mouse hind-paw: modulation by simultaneous ETB receptor activation. Br J Pharmacol 129(5):961

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Werner MFP, Trevisani M, Campi B, André E, Geppetti P, Rae GA (2010) Contribution of peripheral endothelin ETA and ETB receptors in neuropathic pain induced by spinal nerve ligation in rats. Eur J Pain 14(9):911–917

    Article  CAS  PubMed  Google Scholar 

  7. Khodorova A, Navarro B, Jouaville LS, Murphy JE, Rice FL, Mazurkiewicz JE, Long-Woodward D, Stoffel M et al (2003) Endothelin-B receptor activation triggers an endogenous analgesic cascade at sites of peripheral injury. Nat Med 9:1055–1061

    Article  CAS  PubMed  Google Scholar 

  8. Khodorova A, Zou S, Ren K, Dubner R, Davar G, Strichartz G (2009) Dual roles for endothelin-B receptors in modulating adjuvant-induced inflammatory hyperalgesia in rats. Open Pain J 2:30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 117(4):500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Feng B, Strichartz G (2009) Endothelin-1 raises excitability and reduces potassium currents in sensory neurons. Brain Res Bull 79(6):345–350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Smith TP, Smith SN, Sweitzer SM (2014) Endothelin-1 induced desensitization in primary afferent neurons. Neurosci Lett 582:59–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhou Z, Davar G, Strichartz G (2002) Endothelin-1 (ET-1) selectively enhances the activation gating of slowly inactivating tetrodotoxin-resistant sodium currents in rat sensory neurons: a mechanism for the pain-inducing actions of ET-1. J Neurosci 22(15):6325–6330

    CAS  PubMed  Google Scholar 

  13. Ono K, Tsujimoto G, Sakamoto A, Eto K, Masaki T, Ozaki Y, Satake M (1994) Endothelin-A receptor mediates cardiac inhibition by regulating calcium and potassium currents. Nature 370(6487):301–314

  14. Seyler C, Duthilâ SE, Zitron E, Gierten J, Scholz EP, Fink RHA, Karle CA, Becker R et al (2012) TASK1 (K2P3.1) K+ channel inhibition by endothelin-1 is mediated through Rho kinase dependent phosphorylation. Br J Pharmacol 165(5):1467–1475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Shimoda LA, Sylvester JT, Sham JSK (1998) Inhibition of voltage-gated K+ current in rat intrapulmonary arterial myocytes by endothelin-1. Am J Phys Lung Cell Mol Phys 274(5):L842–L853

    CAS  Google Scholar 

  16. Barr TP, Kam S, Khodorova A, Montmayeur J-P, Strichartz GR (2011) New perspectives on the endothelin axis in pain. Pharmacol Res 63(6):532–540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lee LK, Kim JH, Kim MY, Lee JU, Yang SM, Jeon HJ, Lee WD, Noh JW et al (2014) A review of signal transduction of endothelin-1 and mitogen-activated protein kinase-related pain for nanophysiotherapy. J Phys Ther Sci 26(5):789–792

  18. Khodorova A, Fareed MU, Gokin A, Strichartz GR, Davar G (2002) Local injection of a selective endothelin-B receptor agonist inhibits endothelin-1-induced pain-like behavior and excitation of nociceptors in a naloxone-sensitive manner. J Neurosci 22(17):7788

    CAS  PubMed  Google Scholar 

  19. Quang PN, Schmidt BL (2010) Peripheral endothelin B receptor agonist-induced antinociception involves endogenous opioids in mice. Pain 149(2):254–262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Quang PN, Schmidt BL (2010) Endothelin-A receptor antagonism attenuates carcinoma-induced pain through opioids in mice. J Pain 11(7):663–671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zheng J-H, Walters ET, Song X-J (2007) Dissociation of dorsal root ganglion neurons induces hyperexcitability that is maintained by increased responsiveness to cAMP and cGMP. J Neurophysiol 97(1):15–25

    Article  CAS  PubMed  Google Scholar 

  22. Chen G, Tanabe K, Yanagidate F, Kawasaki Y, Zhang L, Dohi S, Iida H (2012) Intrathecal endothelin-1 has antinociceptive effects in rat model of postoperative pain. Eur J Pharmacol 697(1-3):40–46

  23. Shrestha S, Gracias NG, Mujenda F, Khodorova A, Vasko MR, Strichartz GR (2009) Local Antinociception induced by endothelin-1 in the hairy skin of the Rat's back. J Pain 10(7):702–714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kharatmal SB, Singh JN, Sharma SS (2015) Rufinamide improves functional and behavioral deficits via blockade of tetrodotoxin-resistant sodium channels in diabetic neuropathy. Curr Neurovasc Res 12(3):262–268

  25. Singh JN, Jain G, Ramarao P, Sharma SS (2009) Inhibition of sodium current by carbamazepine in dorsal root ganglion neurons in vitro. Indian J Physiol Pharmacol 53(2):147–154

    CAS  PubMed  Google Scholar 

  26. Rasband MN, Park EW, Vanderah TW, Lai J, Porreca F, Trimmer JS (2001) Distinct potassium channels on pain-sensing neurons. Proc Natl Acad Sci 98(23):13373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Everill B, Kocsis JD (1999) Reduction in potassium currents in identified cutaneous afferent dorsal root ganglion neurons after axotomy. J Neurophysiol 82(2):700

    Article  CAS  PubMed  Google Scholar 

  28. Liedgens H, Obradovic M, De Courcy J, Holbrook T, Jakubanis R (2016) A burden of illness study for neuropathic pain in Europe. Clinicoecon Outcomes Res: CEOR 8:113

    Google Scholar 

  29. Henschke N, Kamper SJ, Maher CG The epidemiology and economic consequences of pain. In: Mayo Clinic Proceedings, 2015. Elsevier, pp 139–147

  30. Passmore GM (2005) Dorsal root ganglion neurones in culture: A model system for identifying novel analgesic targets? J Pharmacol Toxicol Methods 51(3):201–208

    Article  CAS  PubMed  Google Scholar 

  31. Zhang JM, Donnelly DF, Song XJ, Lamotte RH (1997) Axotomy increases the excitability of dorsal root ganglion cells with unmyelinated axons. J Neurophysiol 78(5):2790–2794

    Article  CAS  PubMed  Google Scholar 

  32. Takeda M, Tsuboi Y, Kitagawa J, Nakagawa K, Iwata K, Matsumoto S (2011) Potassium channels as a potential therapeutic target for trigeminal neuropathic and inflammatory pain. Mol Pain 7(5):1–8

    Google Scholar 

  33. Lawson K (2006) Potassium channels as targets for the management of pain. Cent Nerv Syst Agents Med Chem (Formerly Curr Med) 6(2):119–128

    Article  CAS  Google Scholar 

  34. Kim CH, Oh Y, Chung JM, Chung K (2002) Changes in three subtypes of tetrodotoxin sensitive sodium channel expression in the axotomized dorsal root ganglion in the rat. Neurosci Lett 323(2):125–128

    Article  CAS  PubMed  Google Scholar 

  35. Hong S, Morrow TJ, Paulson PE, Isom LL, Wiley JW (2004) Early painful diabetic neuropathy is associated with differential changes in tetrodotoxin-sensitive and-resistant sodium channels in dorsal root ganglion neurons in the rat. J Biol Chem 279(28):29341–29350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lai J, Porreca F, Hunter JC, Gold MS (2004) Voltage-gated sodium channels and hyperalgesia. Annu Rev Pharmacol Toxicol 44:371–397

    Article  CAS  PubMed  Google Scholar 

  37. Beekwilder JP, O'Leary ME, Van Den Broek LP, Van Kempen GTH, Ypey DL, Van den Berg RJ (2003) Kv1. 1 channels of dorsal root ganglion neurons are inhibited byn-butyl-p-aminobenzoate, a promising anesthetic for the treatment of chronic pain. J Pharmacol Exp Ther 304(2):531

    Article  CAS  PubMed  Google Scholar 

  38. Dost R, Rostock A, Rundfeldt C (2004) The anti-hyperalgesic activity of retigabine is mediated by KCNQ potassium channel activation. Naunyn Schmiedeberg's Arch Pharmacol 369(4):382–390

    Article  CAS  Google Scholar 

  39. Woolf CJ, Mannion RJ (1999) Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 353(9168):1959–1964

    Article  CAS  PubMed  Google Scholar 

  40. Waxman SG, Dib-Hajj S, Cummins TR, Black JA (2000) Sodium channels and their genes: dynamic expression in the normal nervous system, dysregulation in disease states. Brain Res 886(1):5–14

    Article  CAS  PubMed  Google Scholar 

  41. Kim DS, Choi JO, Rim HD, Cho HJ (2002) Downregulation of voltage-gated potassium channel α gene expression in dorsal root ganglia following chronic constriction injury of the rat sciatic nerve. Mol Brain Res 105(1):146–152

    Article  CAS  PubMed  Google Scholar 

  42. Brochu RM, Dick IE, Tarpley JW, McGowan E, Gunner D, Herrington J, Shao PP, Ok D et al (2006) Block of peripheral nerve sodium channels selectively inhibits features of neuropathic pain in rats. Mol Pharmacol 69(3):823–832

    CAS  PubMed  Google Scholar 

  43. Priest BT, Kaczorowski GJ (2007) Blocking sodium channels to treat neuropathic pain. Expert Opin Ther Targets 11(3):291–306

    Article  PubMed  Google Scholar 

  44. Momin A, Wood JN (2008) Sensory neuron voltage-gated sodium channels as analgesic drug targets. Curr Opin Neurobiol 18(4):383–388

    Article  CAS  PubMed  Google Scholar 

  45. Bhattacharya A, Wickenden AD, Chaplan SR (2009) Sodium channel blockers for the treatment of neuropathic pain. Neurotherapeutics 6(4):663–678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Dib-Hajj SD, Cummins TR, Black JA, Waxman SG (2009) Sodium channels in normal and pathological pain. Annu Rev Neurosci 32:1–32

    Article  Google Scholar 

  47. Cummins TR, Sheets PL, Waxman SG (2007) The roles of sodium channels in nociception: Implications for mechanisms of pain. Pain 131(3):243–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kelso E, Spiers P, McDermott B, Scholfield N, Silke B (1996) Dual effects of endothelin-1 on the L-type Ca2+ current in ventricular cardiomyocytes. Eur J Pharmacol 308(3):351–355

    Article  CAS  PubMed  Google Scholar 

  49. James AF, Ramsey JE, Reynolds AM, Hendry BM, Shattock MJ (2001) Effects of endothelin-1 on K+ currents from rat ventricular myocytes. Biochem Biophys Res Commun 284(4):1048–1055

    Article  CAS  PubMed  Google Scholar 

  50. Nakajima T, Hazama H, Hamada E, Wu SN, Igarashi K, Yamashita T, Seyama Y, Omata M et al (1996) Endothelin-1 and vasopressin activate Ca2+-permeable non-selective cation channels in aortic smooth muscle cells: mechanism of receptor-mediated Ca2+ influx. J Mol Cell Cardiol 28(4):707–722

    Article  CAS  PubMed  Google Scholar 

  51. Zeng Q, Zhou Q, Yao F, O'Rourke ST, Sun C (2008) Endothelin-1 regulates cardiac L-type calcium channels via NAD (P) H oxidase-derived superoxide. J Pharmacol Exp Ther 326(3):732–738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kelso EJ, Spiers JP, McDermott BJ, Scholfield CN, Silke B (1998) Stimulation of L-type Ca2+ current by the endothelin receptor A-selective antagonist, BQ-123, in ventricular cardiomyocytes isolated from rabbit myocardium. Biochem Pharmacol 55(6):897–902

    Article  CAS  PubMed  Google Scholar 

  53. Piovezan AP, D'Orléans-Juste P, Tonussi CR, Rae GA (1998) Effects of endothelin-1 on capsaicin-induced nociception in mice. Eur J Pharmacol 351(1):15–22

    Article  CAS  PubMed  Google Scholar 

  54. Hans G, Deseure K, Adriaensen H (2008) Endothelin-1-induced pain and hyperalgesia: a review of pathophysiology, clinical manifestations and future therapeutic options. Neuropeptides 42(2):119–132

    Article  CAS  PubMed  Google Scholar 

  55. Joseph EK, Gear RW, Levine JD (2011) Mechanical stimulation enhances endothelin-1 hyperalgesia. Neuroscience 178:189–195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Hans G, Schmidt BL, Strichartz G (2009) Nociceptive sensitization by endothelin-1. Brain Res Rev 60(1):36–42

    Article  CAS  PubMed  Google Scholar 

  57. Namer B, Hilliges M, Ørstavik K, Schmidt R, Weidner C, Torebjörk E, Handwerker H, Schmelz M (2008) Endothelin1 activates and sensitizes human C-nociceptors. Pain 137(1):41–49

    Article  CAS  PubMed  Google Scholar 

  58. Dahlof B, Gustafsson D, Hedner T, Jernt S, Hansson L (1990) Regional haemodynamic effects of endothelin-1 in rat and man: unexpected adverse reactions. J Hypertens 8(9):811–817

    Article  CAS  PubMed  Google Scholar 

  59. Ferreira S, Romitelli M, De Nucci G (1989) Endothelin-1 participation in overt and inflammatory pain. J Cardiovasc Pharmacol 13:S220

    Article  CAS  PubMed  Google Scholar 

  60. Jarvis MF, Wessale JL, Zhu CZ, Lynch JJ, Dayton BD, Calzadilla SV, Padley RJ, Opgenorth TJ et al (2000) ABT-627, an endothelin ETA receptor-selective antagonist, attenuates tactile allodynia in a diabetic rat model of neuropathic pain. Eur J Pharmacol 388(1):29–35

    Article  CAS  PubMed  Google Scholar 

  61. Yuyama H, Koakutsu A, Fujiyasu N, Tanahashi M, Fujimori A, Sato S, Shibasaki K, Tanaka S et al (2004) Effects of selective endothelin ETA receptor antagonists on endothelin-1-induced potentiation of cancer pain. Eur J Pharmacol 492(2–3):177–182

    Article  CAS  PubMed  Google Scholar 

  62. Motta EM, Chichorro JG, Rae GA (2009) Role of ETA and ETB endothelin receptors on endothelin-1-induced potentiation of nociceptive and thermal hyperalgesic responses evoked by capsaicin in rats. Neurosci Lett 457(3):146–150

    Article  CAS  PubMed  Google Scholar 

  63. Griswold DE, Douglas SA, Martin LD, Davis TG, Davis L, Ao Z, Luttmann MA, Pullen M et al (1999) Endothelin B receptor modulates inflammatory pain and cutaneous inflammation. Mol Pharmacol 56(4):807–812

    CAS  PubMed  Google Scholar 

  64. Lemos TEV, Porto RM, Ribela MT, Camara PRS (2006) ETB receptor activation as a mechanism of modulation of inflammatory pain and neurogenic inflammation in the temporomandibular joint of capsaicin-treated rats. J Exp Integr Med 3(3):191–197

    Article  Google Scholar 

  65. Plant TD, Zöllner C, Kepura F, Mousa SS, Eichhorst J, Schaefer M, Furkert J, Stein C et al (2007) Endothelin potentiates TRPV1 via ET A receptor-mediated activation of protein kinase C. Mol Pain 3(1):1

    Google Scholar 

  66. Eisenberg E, Erlich T, Zinder O, Lichinsky S, Diamond E, Pud D, Davar G (2004) Plasma endothelin-1 levels in patients with complex regional pain syndrome. Eur J Pain 8(6):533–538

    Article  CAS  PubMed  Google Scholar 

  67. Piuhola J, Mäkinen M, Szokodi I, Ruskoaho H (2003) Dual role of endothelin-1 via ETA and ETB receptors in regulation of cardiac contractile function in mice. Am J Phys Heart Circ Phys 285(1):H112–H118

    CAS  Google Scholar 

Download references

Acknowledgements

The authors thank the Department of Pharmaceuticals, Ministry of Chemical and Fertilizers, Government of India, for the financial support.

Author information

Author notes

  1. Nandkishor K. Mule, Jitendra N. Singh, and Kunal U. Shah contributed equally to this study.

Authors and Affiliations

  1. Electrophysiology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab, 160062, India

    Nandkishor K. Mule, Jitendra N. Singh, Kunal U. Shah & Shyam S. Sharma

  2. Department of Pharmaceutical Sciences, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, 60515, USA

    Anil Gulati

Authors
  1. Nandkishor K. Mule
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jitendra N. Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kunal U. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anil Gulati
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shyam S. Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SSS and JNS conceptualized the study design. NKM and KS carried out the experiments. NKM, KS, and JNS analyzed the data. NKM, JNS, SSS, and AG wrote the final version of the manuscript.

Corresponding authors

Correspondence to Jitendra N. Singh or Shyam S. Sharma.

Ethics declarations

All experimental protocols were approved by the Institutional Animal Ethics Committee, National Institute of Pharmaceutical Education and Research, SAS Nagar, India.

Conflict of Interest

The authors declare that they have no conflict of interest.

Electronic Supplementary Material

ESM 1

(PDF 9014 kb)

Typical AP trace recorded from DRG neuron and commonly measured AP parameters are shown (A). The AP was elicited by injection of depolarizing current injections (40 ms pulses) in 20 pA increments (shown in inset); it evoked all-or-none action potential overshoot. The current threshold was defined as the minimum current required to evoke an AP, for instance Ithreshold for this neuron was 0.1 nA. Several AP parameters were calculated for given recording and summarized (B).

ESM 2

(PDF 10692 kb)

The sodium current was elicited by stepping voltage from -50 to 50 mV in 5 mV increment with a pre-pulse of -120 mV for 50 ms (A) is shown. Original traces and voltage pulse protocols used to isolate transient (left panel) and delayed (right panel) component of macroscopic potassium currents recorded from the neonatal rat DRG neurons (B) are shown. Owing to its faster inactivation, the transient component of IK can selectively be rendered inactive by giving pre-pulse of -40 mV. The neurons were clamped at -80 mV and IK were elicited by giving a pre-pulse of (-40 mV for IKDR or -120 mV for IKT) followed by steps from -50 to 60 mV in 10 mV increment.

ESM 3

Schematic diagram depicting dual actions of ET-1 on pro-nociceptive and anti-nociceptive via activation of ETAR and ETBR, respectively. The pro-nociceptive action of ET-1 is mediated via activation of ETAR and underlying secondary messenger system. The anti-nociceptive actions of ET-1 are reportedly carried out via paracrine activation of ETBR in keratinocytes followed by activation of opioid system (as shown in inset, where MOR: Mu opioid receptors system). Here we present an additional non-opioid mechanism of ET-1-mediated anti-nociception which may be orchestrated through the activation of ETBR and resultant modulation of ion channels expressed on DRG neurons. The modulation of ion channels may be carried out via ETBR downstream-secondary messenger system including phospholipase-C (PLC)-inositol trisphosphate (IP3)/diacylglycerol (DAG) system or guanylyl cyclase (GC)/cGMP further employing PKA-PKC to alter the ionic conductances in DRG neurons. (GIF 577 kb)

High Resolution Image (TIFF 2719 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mule, N.K., Singh, J.N., Shah, K.U. et al. Endothelin-1 Decreases Excitability of the Dorsal Root Ganglion Neurons via ETB Receptor. Mol Neurobiol 55, 4297–4310 (2018). https://doi.org/10.1007/s12035-017-0640-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-017-0640-1

Keywords

Search

Navigation