Somatostatin 4 receptor activation modulates G-protein coupled inward rectifying potassium channels and voltage stimulated calcium signals in dorsal root ganglion neurons.
Somatostatin has a wide biological profile resulting from its actions on the five receptor subtypes (sst1-5). Recently somatostatin was shown to exert analgesic effects via activation of the sst4 receptor. Although the analgesia in pain models is established, the precise molecular mechanism has yet to be fully elucidated. This research aimed to identify possible anti-nociceptive mechanisms, showing functional links of the sst4 receptor to G-protein coupled inward rectifying potassium (GIRK) channels and reduction of voltage stimulated calcium influx within the pain processing pathway. Whole cell voltage clamp experiments and calcium imaging experiments were conducted on DRG neurons prepared from adult rats. Application of an sst4 receptor selective agonist, J-2156, on DRG neurons induced a GIRK modulated potassium current, and inhibited voltage sensitive calcium current. Both mechanisms are thought to contribute to the analgesic properties of sst4 receptor agonists.
Boehringer Ingelheim Pharma GmbH & Co. KG, Department of CNS Diseases Research Germany, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany.
Louise
L
Gorham
Boehringer Ingelheim Pharma GmbH & Co. KG, Department of CNS Diseases Research Germany, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany. Electronic address: stefan.just@boehringer-ingelheim.com.
Stefan
S
Just
Boehringer Ingelheim Pharma GmbH & Co. KG, Department of CNS Diseases Research Germany, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany.
Henri
H
Doods
D000818:Animals; D002073:Butanes / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000502:physiology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017481:Receptors, Somatostatin / Q000819:agonists / Q000502:physiology*; D013450:Sulfones / Q000494:pharmacology
D002073:Butanes; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D009281:Naphthalenes; D017481:Receptors, Somatostatin; D013450:Sulfones; C098681:somatostatin receptor subtype-4; C499293:(1'S, 2S)-4-amino-N-(1'-carbamoyl-2'-phenylethyl)-2-(4''-methyl-1''-naphthalenesulfonylamino)butanamide; D002118:Calcium
Ca(v); Dorsal root ganglion; GIRK; GPCR; Somatostatin agonist J-2145; Sst(4) receptor