Protective Effects of PACAP in Peripheral Organs

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide widely distributed in the nervous system, where it exerts strong neuroprotective effects. PACAP is also expressed in peripheral organs but its peripheral protective effects have not been summarized so far. Therefore, the aim of the present paper is to review the existing literature regarding the cytoprotective effects of PACAP in non-neuronal cell types, peripheral tissues, and organs. Among others, PACAP has widespread expression in the digestive system, where it shows protective effects in various intestinal pathologies, such as duodenal ulcer, small bowel ischemia, and intestinal inflammation. PACAP is present in both the exocrine and endocrine pancreas as well as liver where it reduces inflammation and steatosis by interfering with hepatic pathology related to obesity. It is found in several exocrine glands and also in urinary organs, where, with its protective effects being mainly published regarding renal pathologies, PACAP is protective in numerous conditions. PACAP displays anti-inflammatory effects in upper and lower airways of the respiratory system. In the skin, it is involved in the development of inflammatory pathology such as psoriasis and also has anti-allergic effects in a model of contact dermatitis. In the non-neuronal part of the visual system, PACAP showed protective effects in pathological conditions of the cornea and retinal pigment epithelial cells. The positive role of PACAP has been demonstrated on the formation and healing processes of cartilage and bone where it also prevents osteoarthritis and rheumatoid arthritis development. The protective role of PACAP was also demonstrated in the cardiovascular system in different pathological processes including hyperglycaemia-induced endothelial dysfunction and age-related vascular changes. In the heart, PACAP protects against ischemia, oxidative stress, and cardiomyopathies. PACAP is also involved in the protection against the development of pre-senile systemic amyloidosis, which is presented in various peripheral organs in PACAP-deficient mice. The studies summarized here provide strong evidence for the cytoprotective effects of the peptide. The survival-promoting effects of PACAP depend on a number of factors which are also shortly discussed in the present review.

PACAP and PAC1 Receptor Expression in Human Insulinomas

“…The participation of PACAP in tumour growth is varying depending on the cell type, differentiation stage of the tumour and PACAP concentration. Thus, while PACAP stimulates growth of some tumour cells due to its antiapoptotic actions, it inhibits proliferation of other tumour cell types and was even found to inhibit migration of malignant cells (Moody et al 2020;Toth et al 2020). Several environmental circumstances also influence the exact effect of PACAP.…”

PACAP-38 in Acute ST-Segment Elevation Myocardial Infarction in Humans and Pigs: A Translational Study

“…PACAP-38 is the dominant form in mammals. In the last three decades numerous studies have examined the protective effect of PACAP in several ischemic diseases based on its antiapoptotic, anti-inflammatory and general cytoprotective effects [ 12 , 13 , 14 ], suggesting the applicability of PACAP as a potential cardiac biomarker, especially in pathologies with ischemic etiology [ 15 , 16 , 17 , 18 ]. Moreover, a general anti-ischemic effect of PACAP was also proved in the brain [ 19 , 20 , 21 ], in retinal diseases [ 22 , 23 ] and in different peripheral organs, like small intestine, kidney and liver [ 21 , 24 , 25 , 26 ].…”

PACAP is Protective Against Cellular Stress in Retinal Pigment Epithelial Cells

“…Pituitary adenylate cyclase activating polypeptid (PACAP) is a neuropeptide with various functions throughout the whole body and it seems to be an important neurotrophic agent with a general cytoprotective effect (Gaal et al 2008;Toth et al 2020;Maugeri et al 2020a;Szegeczki et al 2019;Girard et al 2020;Martínez-Rojas et al 2020). PACAP is widely distributed not only in the central nervous system, but in the periphery as well, exerting several beneficial actions.…”