Pituitary Adenylate Cyclase-Activating Polypeptide in the Auditory System

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with well-known neurotrophic, neuroprotective, antioxidant, and antiapoptotic effects. It also exerts protective effects in sensory organs, such as visual and olfactory system. In this review we present data regarding the localization and effects of PACAP in the auditory system. PACAP and its specifi c receptor (PAC1-R) are present in the organ of Corti in hair cells, supporting cells, and different nerve fi bers. They are also present in the spiral ganglion showing co-localization with efferent fi bers of glutamatergic and adrenergic pathways, probably directly affecting the efferent signal transduction in the inner ear. PACAP and its specifi c receptor also occur in the stria vascularis suggesting a role in endolymph production; furthermore, they are present in central pathways of the auditory system such as the cochlear nuclei, superior olivary complex, inferior colliculus, and medial geniculate body. PAC1-receptor is also present in the inner ear in PACAP-defi cient mice, occurring at the same localization but with altered expression compared to wildtype mice. PACAP protects hair cells from H 2 O 2 -induced apoptosis in chicken inner ear cell cultures in vitro, and the lack of PACAP affects the Ca 2+ -binding protein expression in hair cells in PACAP-defi cient mice under control circumstances and after ototoxic drug treatment.

Diagnostic and Prognostic Value of PACAP in Multiple Myeloma

“…In recent years, significant alterations of this peptide have been detected in human tissues under various physiological and pathological conditions (e.g., neurological disorders: Parkinson's disease, posttraumatic stress disorder; cardiac disorders: cardiomyopathies, acute myocardial infarction; kidney disorders: nephrotic syndrome, nephrectomy), in addition to various malignant disorders. These results suggest a potential role of PACAP in the diagnosis, prognosis, and clinical therapy of certain diseases [11,[20][21][22].…”

“…PACAP is a multifunctional neuropeptide with proven anti-inflammatory, antioxidant, and immunomodulatory effects. The level of endogenous PACAP varies considerably in different diseases, so changes in PACAP levels serve as diagnostic and prognostic markers and may also be helpful in planning clinical therapies for certain diseases [11]. In malignancies, a decrease in the tissue PACAP level was described in colon carcinoma [45], non-small cell lung cancer [45], renal tumors [46], papillary thyroid carcinoma [47], pituitary adenoma [48], pancreatic ductal adenocarcinoma [49], and insulinoma [50], while an increase was observed in neuroblastoma [51,52], ductal and lobular breast carcinoma [53], cervical cancer [54], and prostate tumor [46].…”

“…Pituitary adenylate cyclase-activating polypeptide (PACAP) has well-known immunomodulatory, anti-inflammatory, and antioxidant effects, therefore, it could be one of the most promising markers in the future [11,12]. The peptide was discovered in 1989 [13] and belongs to the vasoactive intestinal peptide (VIP)/secretin/glucagon peptide family [14].…”