title: Somatostatin 4 receptor activation modulates TRPV1[correction of TPRV1] currents in dorsal root ganglion neurons.
abstract: Somatostatin (sst) is a cyclic neuropeptide known to have inhibitory roles in the central nervous system. It exerts its biological effects via the activation of the 5 sst receptor subtypes, which belong to the family of G-protein coupled receptors (GPCR). This peptide has analgesic properties, specifically via the activation of the sst4 receptor subtype. Although this is established, the precise molecular mechanisms causing this have not yet been fully elucidated. This research aimed to identify a possible anti-nociceptive mechanism, showing functional links to the transient receptor potential vanilloid type 1 (TRPV1) within the pain processing pathway. Calcium imaging and whole cell voltage clamp experiments were conducted on DRG neurons prepared from adult rats, utilizing capsaicin stimulations and the sst4 receptor specific agonist J-2156. The complete Freund's adjuvant (CFA) inflammatory pain model was used to examine if effects are augmented in pain conditions. The sst4 receptor agonist J-2156 was able significantly to inhibit capsaicin induced calcium and sodium influx, where the effect was more potent after CFA treatment. This inhibition identifies a contributory molecular mechanism to the analgesic properties of sst4 receptor activation.
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Dept. CNS Diseases Research Germany, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany. Electronic address: louise_catherine_josephine.gorham@boehringer-ingelheim.com.
authors.forename: Louise
authors.initials: L
authors.lastname: Gorham
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Dept. CNS Diseases Research Germany, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Just
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Dept. CNS Diseases Research Germany, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany.
authors.forename: Henri
authors.initials: H
authors.lastname: Doods
mesh_terms: D000818:Animals; D002073:Butanes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D005620:Freund's Adjuvant; D005727:Ganglia, Spinal / Q000187:drug effects / Q000503:physiopathology*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D059225:Nociception; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D037342:Pertussis Toxin / Q000494:pharmacology; D051381:Rats; D017481:Receptors, Somatostatin / Q000819:agonists / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000819:agonists / Q000502:physiology*
chemical_list: D002073:Butanes; D009281:Naphthalenes; D017481:Receptors, Somatostatin; D013450:Sulfones; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C098681:somatostatin receptor subtype-4; D005620:Freund's Adjuvant; D037342:Pertussis Toxin; C499293:(1'S, 2S)-4-amino-N-(1'-carbamoyl-2'-phenylethyl)-2-(4''-methyl-1''-naphthalenesulfonylamino)butanamide; D002211:Capsaicin; D002118:Calcium
keywords: DRG; GPCR; Somatostatin agonist J-2145; TRPV1; sst(4) Receptor