title: Role of somatostatin receptor-2 in gentamicin-induced auditory hair cell loss in the Mammalian inner ear.
abstract: Hair cells and spiral ganglion neurons of the mammalian auditory system do not regenerate, and their loss leads to irreversible hearing loss. Aminoglycosides induce auditory hair cell death in vitro, and evidence suggests that phosphatidylinositol-3-kinase/Akt signaling opposes gentamicin toxicity via its downstream target, the protein kinase Akt. We previously demonstrated that somatostatin-a peptide with hormone/neurotransmitter properties-can protect hair cells from gentamicin-induced hair cell death in vitro, and that somatostatin receptors are expressed in the mammalian inner ear. However, it remains unknown how this protective effect is mediated. In the present study, we show a highly significant protective effect of octreotide (a drug that mimics and is more potent than somatostatin) on gentamicin-induced hair cell death, and increased Akt phosphorylation in octreotide-treated organ of Corti explants in vitro. Moreover, we demonstrate that somatostatin receptor-1 knockout mice overexpress somatostatin receptor-2 in the organ of Corti, and are less susceptible to gentamicin-induced hair cell loss than wild-type or somatostatin-1/somatostatin-2 double-knockout mice. Finally, we show that octreotide affects auditory hair cells, enhances spiral ganglion neurite number, and decreases spiral ganglion neurite length.
authors.affiliation: Department of Biomedicine, University Hospital Basel, Basel, Switzerland and Clinic for Otolaryngology, Head and Neck Surgery, University Hospital Basel, Basel, Switzerland.
authors.forename: Yves
authors.initials: Y
authors.lastname: Brand
authors.affiliation: Department of Biomedicine, University Hospital Basel, Basel, Switzerland and Clinic for Otolaryngology, Head and Neck Surgery, University Hospital Basel, Basel, Switzerland.
authors.forename: Vesna
authors.initials: V
authors.lastname: Radojevic
authors.affiliation: Department of Biomedicine, University Hospital Basel, Basel, Switzerland and Clinic for Otolaryngology, Head and Neck Surgery, University Hospital Basel, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Sung
authors.affiliation: Department of Biomedicine, University Hospital Basel, Basel, Switzerland and Clinic for Otolaryngology, Head and Neck Surgery, University Hospital Basel, Basel, Switzerland.
authors.forename: Eric
authors.initials: E
authors.lastname: Wei
authors.affiliation: Department of Biomedicine, University Hospital Basel, Basel, Switzerland and Clinic for Otolaryngology, Head and Neck Surgery, University Hospital Basel, Basel, Switzerland.
authors.forename: Cristian
authors.initials: C
authors.lastname: Setz
authors.affiliation: Department of Biomedicine, University Hospital Basel, Basel, Switzerland and Clinic for Otolaryngology, Head and Neck Surgery, University Hospital Basel, Basel, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Glutz
authors.affiliation: Department of Biomedicine, University Hospital Basel, Basel, Switzerland and Clinic for Otolaryngology, Head and Neck Surgery, University Hospital Basel, Basel, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Leitmeyer
authors.affiliation: Department of Biomedicine, University Hospital Basel, Basel, Switzerland and Clinic for Otolaryngology, Head and Neck Surgery, University Hospital Basel, Basel, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bodmer
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D005786:Gene Expression Regulation; D005839:Gentamicins; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D034381:Hearing Loss / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control; D051379:Mice; D018345:Mice, Knockout; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015282:Octreotide / Q000494:pharmacology; D009924:Organ Culture Techniques; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000172:deficiency / Q000235:genetics*; D015398:Signal Transduction; D013136:Spiral Ganglion / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D005839:Gentamicins; D020011:Protective Agents; D017481:Receptors, Somatostatin; C570770:somatostatin receptor 1, mouse; C570769:somatostatin receptor 2, mouse; D051057:Proto-Oncogene Proteins c-akt; D015282:Octreotide