Disease relevance of ADCYAP1

• The growth rate of rodent embryonic neuroblasts and human neuroblastoma cell lines is regulated in part by autocrine or paracrine actions of neuropeptides of the family that includes vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), and pituitary adenylate cyclase-activating peptide (PACAP) [1].
• Reduction in the activity of PMNs to respond to PACAP was observed after cell exposure to inhibitors of the cAMP/protein kinase A, protein kinase C, and PI3K pathways, to pertussis toxin, genistein, and after chelation of intracellular calcium or after extracellular calcium depletion [2].
• These data demonstrate the presence in human Y-79 retinoblastoma cells of specific PACAP receptors and provide further evidence that PACAP may act as a neurotransmitter/neuromodulator in mammalian retina [3].
• Neuroendocrine differentiation of the LNCaP prostate cancer cell line maintains the expression and function of VIP and PACAP receptors [4].
• Expression of mRNA for PACAP and its receptors in intra- and extra-adrenal human pheochromocytomas and their relationship to catecholamine synthesis [5].

Psychiatry related information on ADCYAP1

• The patients suffer from severe mental retardation and have a bleeding tendency with mild thrombocytopenia, and their fibroblasts show increased PACAP mRNA levels [6].
• Pituitary adenylate cyclase-activating polypeptide (PACAP) and the proopiomelanocortin (POMC)-derived peptide alpha-melanocyte-stimulating hormone (alpha-MSH) both regulate multiple neuroendocrine functions and feeding behavior [7].
• Recent evidence indicates that pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) might play an important role in rapid eye movement sleep (REMS) generation at the pontine level in rats [8].
• This study did not provide evidence for the contribution of the PACAP gene to the etiology of schizophrenia or bipolar disorders in the Japanese population [9].
• However, after castration, PACAP led only to a slight amelioration of the behavioral symptoms [10].

High impact information on ADCYAP1

• The pituitary adenylate cyclase-activating polypeptide (PACAP)/ glucagon superfamily includes nine hormones in humans that are related by structure, distribution (especially the brain and gut), function (often by activation of cAMP), and receptors (a subset of seven-transmembrane receptors) [11].
• The diverse functions of PACAP include regulation of proliferation, differentiation, and apoptosis in some cell populations [11].
• In addition, PACAP regulates metabolism and the cardiovascular, endocrine, and immune systems, although the physiological event(s) that coordinates PACAP responses remains to be identified [11].
• Pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP/vasoactive intestinal polypeptide receptors: actions on the anterior pituitary gland [12].
• This report reviews the current knowledge concerning the multiple actions of PACAP in the central nervous system and in various peripheral organs including the endocrine glands, the airways, and the cardiovascular and immune systems, as well as the different effects of PACAP on a number of tumor cell types [13].

Chemical compound and disease context of ADCYAP1

• Here we used the androgen-dependent human prostate cancer cell line LNCaP to perform a systematic and broad analysis of the expression, pharmacology, and functionality of vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating peptide (PACAP) receptors [4].
• The findings demonstrate the presence of functional PACAP type I receptors on ciliary ganglion neurons that preferentially recognize PACAP38 and -27 over VIP and act via adenylate cyclase to initiate cAMP-dependent enhancement of AChR function [14].
• These data suggest that the effects of PACAP on the gonadotropin-releasing hormone neuroendocrine axis and the regulation of feeding behavior may be mediated, at least in part, through modulation of POMC neurons [7].
• Moreover, PACAP was found in substance P (SP)-containing ureteral nerve fibres and in SP-containing dorsal root ganglion neurons [15].
• Retinoic acid regulation of the VIP and PACAP autocrine ligand and receptor system in human neuroblastoma cell lines [16].

Biological context of ADCYAP1

• The ADCYAP1 gene is located on chromosome 18p11 linked to type 2 diabetes [17].
• The G allele frequencies of g.9863G>A (G54D) and g.12712C>G of the ADCYAP1 gene were higher in type 2 diabetic patients than in non-diabetic control subjects (21.0% vs 15.8%, P=0.04; 5.3% vs 3.0%, P=0.045) [17].
• Two novel SNPs, g.9863G>A (G54D) in exon 3 and g.12712C>G in the 3'-UTR of exon 5 of the ADCYAP1 gene (accession number X60435), were found [17].
• Genetic variation screening and association studies of the adenylate cyclase activating polypeptide 1 (ADCYAP1) gene in patients with type 2 diabetes [17].
• Dinucleotide repeat polymorphism at the human pituitary adenylate cyclase activating polypeptide (PACAP) gene [18].

Anatomical context of ADCYAP1

• VIP/PACAP inhibit NF-kappa B transactivation in the lipopolysaccharide-stimulated human monocytic cell line THP-1 at multiple levels [19].
• This study shows that in human polymorphonuclear neutrophils (PMNs), PACAP acts as a proinflammatory molecule [20].
• Anti-inflammatory activities of pituitary adenylate cyclase-activating protein (PACAP) are mediated in part through specific effects on lymphocytes and macrophages [20].
• The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) suppress monocyte/macrophage production of proinflammatory agents [19].
• In intact cells, both PACAPs and VIP failed to stimulate the phosphoinositide hydrolysis, whereas in cell membranes PACAP 38, but not the other peptides, produced a modest increase (40%) of inositol phosphate formation with an EC50 value of 22 nM [3].

Associations of ADCYAP1 with chemical compounds

• Adenylate cyclase activating polypeptide 1 (ADCYAP1) is a pancreatic neuropeptide and modulates glucose-stimulated insulin secretion [17].
• In PMNs, PACAP increases cAMP, inositol triphosphate metabolites, and calcium [20].
• In these cells, PACAP increases TrkA tyrosine phosphorylations through a PI-3kinase dependent but phospholipase C independent pathway [21].
• Firstly, we found that ICV injections of PACAP and VIP increased plasma corticosterone concentrations [22].
• The most fascinating role for PACAP is, however, its auto- or paracrine function in the peri- and postovulatory events involving acute progesterone production and subsequent luteinization in periovulatory granulosa/lutein cells [23].

Physical interactions of ADCYAP1

• In conclusion, this study clearly demonstrates the expression of VIP/PACAP common receptors associated with alpha s protein in human prostate and suggests that these neuropeptides could play an important and complex role in the physiology and pathophysiology of this human gland [24].
• A DISC1-binding domain of DBZ reduced the neurite length in PC12 cells after PACAP stimulation and in primary cultured hippocampal neurons [25].

Enzymatic interactions of ADCYAP1

• In the short precursor, the coding region for GHRH is deleted leaving the PACAP-coding region in a correct reading frame [26].

Co-localisations of ADCYAP1

• 7. The results suggest that PACAP and Hel-1 are co-localized with VIP in nerve structures within the human cavernous tissue, and that the peptides are effective relaxants of CC preparations in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)[27]
• PACAP was found to be co-localized with ChAT in nerve fibers of the intraganglionic spiral bundle and beneath the inner and outer hair cells within the organ of Corti [28].
• PACAP and melanopsin were colocalized in the RGCs and PACAP-containing nerve fibers, seemingly innervating the retinorecipient part of the SCN [29].

Regulatory relationships of ADCYAP1

• Thus PACAP and PACAP-27 potently stimulate colonocyte ion transport via mechanisms mediated by the VIP receptor and cAMP-dependent signaling [30].
• These data show for the first time in humans that ACTH and PRL secretions from the anterior pituitary gland are stimulated by the systemic administration of PACAP [31].
• VIP but not PACAP also exerts a weak direct secretagogue action on adrenocortical cells by activating both PVRs and probably a subtype of ACTH receptors [32].
• Galanin and the newly discovered peptides helospectin and pituitary adenylate cyclase activating peptide (PACAP) could not be detected in human salivary glands [33].
• Studies of the genes encoding the PACAP precursor and the type I PACAP receptor provide information on the control of PACAP gene expression and on the relationship between the structure of the receptor subtypes and the activation of various signal transduction pathways [34].

Other interactions of ADCYAP1

• Since NF-kappaB represents a focal point for various stimuli and induces the expression of many proinflammatory genes, its targeting by VIP and PACAP positions them as important anti-inflammatory agents [19].
• Pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-receptor type 1 expression in rat and human placenta [35].
• Pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin, and gastrin receptor expression was determined by real-time RT-PCR [36].
• Both PACAP and NGF have pro-inflammatory activities on monocytes [21].
• However, neither in tissues nor cell lines did PACAP mRNA expression correlate with TH mRNA expression [37].

Analytical, diagnostic and therapeutic context of ADCYAP1

• Northern blot analysis revealed gene expression for only the PACAP-preferring (PAC1) receptor [1].
• In the present study, we show the expression of PACAP gene and irPACAP distribution within rat and human placental tissues, by means of RT-PCR and immunohystochemical experiments [35].
• In conclusion, using improved immunocytochemistry techniques and electron microscopy (EM), PACAP was shown to be expressed both in normal and diabetic islet cells and localized to secretory granules of insulin and glucagon cells [38].
• To that end, PACAP immunoreactivity was studied by immunofluorescence methods enhanced by the catalyzed reporter deposition (CARD) technique [38].
• Receptor autoradiography showed PACAP types I and II binding sites in all groups of pituitary adenomas, except prolactinomas [39].

References