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Roles of Cav3.2 and TRPA1 channels targeted by hydrogen sulfide in pancreatic nociceptive processing in mice with or without acute pancreatitis.
J Neurosci Res. 2015 Feb; 93(2):361-9.JN

Abstract

Hydrogen sulfide (H(2)S), formed by multiple enzymes, including cystathionine-γ-lyase (CSE), targets Ca(v)3.2 T-type Ca(2+) channels (T channels) and transient receptor potential ankyrin-1 (TRPA1), facilitating somatic pain. Pancreatitis-related pain also appears to involve activation of T channels by H(2)S formed by the upregulated CSE. Therefore, this study investigates the roles of the Ca(v)3.2 isoform and/or TRPA1 in pancreatic nociception in the absence and presence of pancreatitis. In anesthetized mice, AP18, a TRPA1 inhibitor, abolished the Fos expression in the spinal dorsal horn caused by injection of a TRPA1 agonist into the pancreatic duct. As did mibefradil, a T-channel inhibitor, in our previous report, AP18 prevented the Fos expression following ductal NaHS, an H(2)S donor. In the mice with cerulein-induced acute pancreatitis, the referred hyperalgesia was suppressed by NNC 55-0396 (NNC), a selective T-channel inhibitor; zinc chloride; or ascorbic acid, known to inhibit Ca(v)3.2 selectively among three T-channel isoforms; and knockdown of Ca(v)3.2. In contrast, AP18 and knockdown of TRPA1 had no significant effect on the cerulein-induced referred hyperalgesia, although they significantly potentiated the antihyperalgesic effect of NNC at a subeffective dose. TRPA1 but not Ca(v)3.2 in the dorsal root ganglia was downregulated at a protein level in mice with cerulein-induced pancreatitis. The data indicate that TRPA1 and Ca(v)3.2 mediate the exogenous H(2)S-induced pancreatic nociception in naïve mice and suggest that, in the mice with pancreatitis, Ca(v)3.2 targeted by H(2)S primarily participates in the pancreatic pain, whereas TRPA1 is downregulated and plays a secondary role in pancreatic nociceptive signaling.

Authors+Show Affiliations

Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, Higashi-Osaka, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25267397

Citation

Terada, Yuka, et al. "Roles of Cav3.2 and TRPA1 Channels Targeted By Hydrogen Sulfide in Pancreatic Nociceptive Processing in Mice With or Without Acute Pancreatitis." Journal of Neuroscience Research, vol. 93, no. 2, 2015, pp. 361-9.
Terada Y, Fujimura M, Nishimura S, et al. Roles of Cav3.2 and TRPA1 channels targeted by hydrogen sulfide in pancreatic nociceptive processing in mice with or without acute pancreatitis. J Neurosci Res. 2015;93(2):361-9.
Terada, Y., Fujimura, M., Nishimura, S., Tsubota, M., Sekiguchi, F., & Kawabata, A. (2015). Roles of Cav3.2 and TRPA1 channels targeted by hydrogen sulfide in pancreatic nociceptive processing in mice with or without acute pancreatitis. Journal of Neuroscience Research, 93(2), 361-9. https://doi.org/10.1002/jnr.23490
Terada Y, et al. Roles of Cav3.2 and TRPA1 Channels Targeted By Hydrogen Sulfide in Pancreatic Nociceptive Processing in Mice With or Without Acute Pancreatitis. J Neurosci Res. 2015;93(2):361-9. PubMed PMID: 25267397.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Roles of Cav3.2 and TRPA1 channels targeted by hydrogen sulfide in pancreatic nociceptive processing in mice with or without acute pancreatitis. AU - Terada,Yuka, AU - Fujimura,Mayuko, AU - Nishimura,Sachiyo, AU - Tsubota,Maho, AU - Sekiguchi,Fumiko, AU - Kawabata,Atsufumi, Y1 - 2014/09/30/ PY - 2014/06/03/received PY - 2014/07/05/revised PY - 2014/09/07/accepted PY - 2014/10/1/entrez PY - 2014/10/1/pubmed PY - 2015/8/20/medline KW - Cav3.2 T-type calcium channel KW - TRPA1 KW - hydrogen sulfide KW - pancreatic pain KW - pancreatitis SP - 361 EP - 9 JF - Journal of neuroscience research JO - J Neurosci Res VL - 93 IS - 2 N2 - Hydrogen sulfide (H(2)S), formed by multiple enzymes, including cystathionine-γ-lyase (CSE), targets Ca(v)3.2 T-type Ca(2+) channels (T channels) and transient receptor potential ankyrin-1 (TRPA1), facilitating somatic pain. Pancreatitis-related pain also appears to involve activation of T channels by H(2)S formed by the upregulated CSE. Therefore, this study investigates the roles of the Ca(v)3.2 isoform and/or TRPA1 in pancreatic nociception in the absence and presence of pancreatitis. In anesthetized mice, AP18, a TRPA1 inhibitor, abolished the Fos expression in the spinal dorsal horn caused by injection of a TRPA1 agonist into the pancreatic duct. As did mibefradil, a T-channel inhibitor, in our previous report, AP18 prevented the Fos expression following ductal NaHS, an H(2)S donor. In the mice with cerulein-induced acute pancreatitis, the referred hyperalgesia was suppressed by NNC 55-0396 (NNC), a selective T-channel inhibitor; zinc chloride; or ascorbic acid, known to inhibit Ca(v)3.2 selectively among three T-channel isoforms; and knockdown of Ca(v)3.2. In contrast, AP18 and knockdown of TRPA1 had no significant effect on the cerulein-induced referred hyperalgesia, although they significantly potentiated the antihyperalgesic effect of NNC at a subeffective dose. TRPA1 but not Ca(v)3.2 in the dorsal root ganglia was downregulated at a protein level in mice with cerulein-induced pancreatitis. The data indicate that TRPA1 and Ca(v)3.2 mediate the exogenous H(2)S-induced pancreatic nociception in naïve mice and suggest that, in the mice with pancreatitis, Ca(v)3.2 targeted by H(2)S primarily participates in the pancreatic pain, whereas TRPA1 is downregulated and plays a secondary role in pancreatic nociceptive signaling. SN - 1097-4547 UR - https://www.unboundmedicine.com/medline/citation/25267397/Roles_of_Cav3_2_and_TRPA1_channels_targeted_by_hydrogen_sulfide_in_pancreatic_nociceptive_processing_in_mice_with_or_without_acute_pancreatitis_ L2 - https://doi.org/10.1002/jnr.23490 DB - PRIME DP - Unbound Medicine ER -