Abstract
Prostaglandin E1 (PGE1) is frequently used for the clinical treatment of acute sensorineural hearing loss. However, the mechanisms underlying the effects of PGE1 in the inner ear have not yet been elucidated. The physiological effects of PGE1 are mediated by four distinct E-prostanoidreceptor (EP) subtypes namely EP1, EP2, EP3, and EP4. Signal transduction pathway of EP subtypes has been studied. EP1 couples to Gq protein resulting in the elevation of the free Ca+ concentration. EP2 and EP4 receptors couple to Gs and mediate increases in intracellular cAMP levels. In contrast, EP3 couples to Gi for signaling resulting in decreased cAMP concentration. Furthermore, the ligand binding specificities of mouse prostanoid receptors have been examined. The rank order of affinity of PGE1 for four receptors was EP3≥EP4>EP2>EP1. In the current study, we examined EP subtypes expression in the mouse inner ear using the reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in order to elucidate the mechanisms underlying the effects of PGE1 in the inner ear.
Male C57BL/6 mice at 8 weeks of age were used for the present studies. The results of RT-PCR demonstrated EP subtypes mRNA expression in the mouse cochleae. Immunohistochemistry for the cochleae demonstrated EP1 expression in the hair cells (HCs) and supporting cells (SCs), EP2 and EP4 expression occurred in the HCs, SCs, spiral ligament, stria vasculis, and spiral ganglion cells. EP3 expression occurred in the HCs, SCs, spiral ligament, and spiral ganglion cells. Immunohistochemistry for the vestibule and semicircular canals demonstrated four EP subtypes expression in the sensory epithelia of the vestibule and semicircular canals.
Previous studies have indicated the involvement of EP4 in the physiopathology of cochleae and the therapeutic capability of EP4 agonists for noise-induced hearing loss. Considering binding specificities of PGE1 to four EP subtypes and localization of EP subtypes in the inner ear, EP2 and EP4 may be involved in therapeutic effects of PGE1 in the cochlea, and the stimulation of EP3 by PGE1 may contradict effects of EP2 and EP4 stimulation by PGE1.
