PACAP (hipofízis adenilát-cikláz aktiváló polipeptid) fogfejlődésre gyakorolt hatásainak vizsgálata állatmodellen

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide with widespread distribution. It was first isolated from ovine hypothalamic extract on the basis of its ability to stimulate cAMP formation. PACAP is a member of the vasoactive intestinal polypeptide (VIP)/secretin/growth hormone releasing hormone/glucagon superfamily, with two known bioactive variants: PACAP-27 and PACAP-38. PACAP has the most conserved amino acid sequence in the superfamily, suggesting that it plays an important role in the regulation of basic physiologic functions. Three receptors have been identified so far: PACAP-specific PAC1 receptor, and PACAP/VIP indifferent VPAC1 and VPAC2 receptors. Alternative splicing of PAC1 receptor results in different ligand binding properties, exhibiting pleiotropic activities. PACAP and PAC1 receptor expression in neuroepithelial cells appears at very early stage of embryonic development. PACAP plays role in the regulation of various signaling cascades in the neuronal cells affecting neurogenesis, neuronal protection, migration, differentiation and the building of neuronal synaptic connections. It is most abundant in the central and peripheral nervous system, nevertheless, the presence of PACAP and its receptors have been shown in non-neuronal tissues, such as the respiratory, urogenital, cardiovascular system, in the ear and in the dental pulp and periodontium. PACAP plays a role in the regulation of various physiological functions, such as thermoregulation, motor activity, nutrition and circadian rhythm. Besides its neurotrophic, neuroprotective and general cytoprotective effect, anti-inflammatory and anti-apoptotic effects are also known. The anti-inflammatory and anti-apoptotic effect could be the background of its general cytoprotective effect in non-neuronal tissues. The possible actions of endogenous PACAP can be studied in PACAP-deficient mice in physiological and pathological conditions. There are no macroscopic differences between wild-type, heterozygous and homozygous PACAP-deficient mice, but with more sophisticated methods (immunohistochemistry, electron microscopy) and functional studies significant alterations can be found. The lack of endogenous PACAP leads to biochemical, behavioral, functional changes and neuronal developmental impairment. Compared to the wild-type mice, PACAP deficient-mice show increased sensitivity against harmful stimuli, such as after bilateral common carotid artery occlusion increased retinal damage could be observed in the PACAP-deficient group.