Prostaglandin E receptor subtype EP4 agonist protects cochleae against noise-induced trauma.
Prostaglandin E(1) is frequently used for the clinical treatment of acute sensorineural hearing loss. However, the mechanisms underlying the effects of prostaglandin E(1) on the inner ear have not yet been elucidated. The physiological effects of prostaglandin E(1) are mediated by the prostanoid receptors prostaglandin I receptor and the prostaglandin E receptor subtypes EP1, EP2, EP3, and EP4, the respective agonists for which have been purified. In the current study, we examined the efficacy of a local EP4 agonist application for the treatment of sensorineural hearing loss. We examined EP4 expression in the mouse cochlea using the reverse transcription-polymerase chain reaction and immunohistochemistry. The protective effects of local EP4 agonist treatment before or after noise exposure were tested in guinea pigs using measurements of auditory brain-stem responses and histological analysis. The results demonstrated EP4 expression in the cochlea, and showed that pre- and post-treatment with an EP4 agonist significantly attenuated threshold shifts of auditory brain stem responses, and significant attenuation in the loss of outer hair cells was found in local EP4 agonist treatment before noise exposure. These findings indicate that EP4 is involved in mechanisms for prostaglandin E(1) actions on the cochlea, and local EP4 agonist treatment could attenuate acute sensorineural hearing loss.
Hori
R
R
Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kawaharacho 54, Shogoin, Sakyo-ku, Kyoto, Japan.
Nakagawa
T
T
Sugimoto
Y
Y
Sakamoto
T
T
Yamamoto
N
N
Hamaguchi
K
K
Ito
J
J
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects / Q000502:physiology; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006319:Hearing Loss, Sensorineural / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology; D009622:Noise / Q000009:adverse effects; D018078:Receptors, Prostaglandin E / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D058309:Receptors, Prostaglandin E, EP4 Subtype; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008738:Methyl Ethers; D018696:Neuroprotective Agents; C461399:ONO-AE1-329; C545651:Ptger4 protein, mouse; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D000527:Alprostadil