title: Hydrogen Sulfide and T-Type Ca2+ Channels in Pain Processing, Neuronal Differentiation and Neuroendocrine Secretion.
abstract: BACKGROUND
  Hydrogen sulfide (H2S), a gasotransmitter, is generated from L-cysteine by mainly 3 enzymes, cystathionine-γ-lyase (CSE), cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase in cooperation with cysteine aminotransferase. The H2S-forming enzymes, particularly CSE, are overexpressed under the pathological conditions such as inflammation, neuronal or neuroendocrine differentiation and cancer development. Given that Cav3.2 T-type Ca2+ channels mediate some of the biological activity of H2S, we focus on the role of the H2S/Cav3.2 pathway in regulating the neuronal and neuroendocrine function.
  
  
  CONCLUSIONS
  In the neuronal system, H2S regulates the activity of various ion channels including Cav3.2. Exogenous and endogenous H2S enhances the Cav3.2 channel activity, promoting somatic and visceral pain signaling. The H2S/Cav3.2 pathway also facilitates neuritogenesis or neuronal differentiation. Interestingly, endogenous H2S formed by CSE regulates secretory function by enhancing Cav3.2 channel activity in neuroendocrine-differentiated prostate cancer cells or carotid glomus cells. Key Messages: The H2S/Cav3.2 pathway may serve as therapeutic targets for treatment of intractable pain, neuronal injury, androgen-independent prostate cancer, cardiovascular diseases, etc.
authors.affiliation: Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University (Formerly Kinki University), Higashi-osaka, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Fukami
authors.forename: Kazuki
authors.initials: K
authors.lastname: Fukami
authors.forename: Fumiko
authors.initials: F
authors.lastname: Sekiguchi
authors.forename: Fumiko
authors.initials: F
authors.lastname: Sekiguchi
authors.forename: Atsufumi
authors.initials: A
authors.lastname: Kawabata
authors.forename: Atsufumi
authors.initials: A
authors.lastname: Kawabata
mesh_terms: D000818:Animals; D020747:Calcium Channels, T-Type / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000502:physiology*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D055099:Neuroendocrine Cells / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010146:Pain / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
chemical_list: D020747:Calcium Channels, T-Type; D006862:Hydrogen Sulfide