Disease relevance of Adcyap1

• PACAP effects on acid secretion were determined in fistula rats with or without neutralizing anti-somatostatin antibodies [1].
• The fact that PACAP prevented ethanol toxicity even when added 2 h after alcohol exposure, suggests that selective PACAP agonists could have potential therapeutic value for the treatment of fetal alcohol syndrome [2].
• In the C6 glioma cell-line, TTF-1 activates the PACAP promoter in a dose-dependent manner [3].
• The effect of PACAP38 on inositol phosphate formation was significantly reduced by U-73122 and by pertussis toxin, indicating that activation of PACAP receptors causes stimulation of a phospholipase C through a pertussis toxin-sensitive G protein [4].
• PACAP was demonstrated in nerve fibres in all compartments of the pancreas and in a subpopulation of intrapancreatic VIP-containing ganglion cells [5].

Psychiatry related information on Adcyap1

• Moreover, injections of PACAP into the centre of the posterior PnO resulted in REM sleep enhancement which could last for up to 11 consecutive days [6].
• The administration of PACAP (1 or 2 nmol) caused a dose-dependent increase in both spontaneous motor activity and rearing behavior in the rat [7].
• We propose that modulation of brain PACAP signaling might represent a new opportunity in the treatment of bipolar disorder [8].
• Water deprivation for 24 h and 48 h caused a significant increase in PACAP gene transcripts in the SFO, compared with euhydrated animals [9].
• The action of pituitary adenylate cyclase activating polypeptide (PACAP) on passive avoidance learning. The role of transmitters [10].

High impact information on Adcyap1

• Differential signal transduction by five splice variants of the PACAP receptor [11].
• Here we have used a new expression cloning strategy, based on the induction of a reporter gene by cyclic AMP, to isolate a complementary DNA encoding the type-I PACAP receptor [11].
• PACAP is an anti-mitogenic signal in developing cerebral cortex [12].
• Genes coding for the neuropeptide hormone pituitary adenylate cyclase activating polypeptide (PACAP) and the enzyme that processes PACAP's precursor to the mature form, peptidylglycine alpha-amidating monooxygenase, were upregulated by inositol depletion [8].
• All splice variants of PAC1 were found, but vasoactive intestinal polypeptide (VIP) receptor (VPAC) products were absent [1].

Chemical compound and disease context of Adcyap1

• The signal transduction pathway mediating VIP- and PACAP-induced potentiation of nicotinic ACh-evoked currents involves a pertussis toxin (PTX)-sensitive G-protein [13].
• Treatment of cells by pertussis toxin (25 ng.mL-1.day-1) suppressed PACAP-stimulated AR4-2J cell growth but enhanced PACAP-induced stimulation of adenylate cyclase activity [14].
• Due to the stimulatory function of PACAP on pineal melatonin secretion, the PACAP-containing neurons of this ganglion could be considered a subset of the parasympathetic nervous system [15].
• PACAP was more potent and longer-lasting than a known potent stimulating peptide, thyrotropin-releasing hormone, in both stimulating motor activity and counteracting reserpine-induced hypothermia [7].
• RESULTS: PACAP augmented caerulein-induced pancreatitis and failed to ameliorate sodium taurocholate-induced pancreatitis [16].

Biological context of Adcyap1

• In this study, we evaluated the effects of two related neuropeptides, pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP), on ECL cell proliferation and characterized the receptor subtype(s) and signal transduction pathways that mediate this effect [17].
• Reverse-transcription polymerase chain reaction (RT-PCR) with gene-specific oligonucleotide primers was performed to characterize the PACAP/VIP receptor subtype(s) [17].
• Transient transfection of gonadotrope-derived alphaT3-1 cells with a rat follistatin promoter-luciferase reporter plasmid reveals that PACAP stimulates follistatin gene transcription [18].
• These studies identified a reciprocal relationship between PVN PACAP and FSHbeta gene expression in maturing rats [19].
• Pacap mRNA expression in the PVN and pituitary varied significantly during the estrous cycle, with the greatest changes occurring on the day of proestrus [20].

Anatomical context of Adcyap1

• Pituitary adenylate cyclase-activating polypeptide modulates gastric enterochromaffin-like cell proliferation in rats [17].
• To elucidate the structural domains involved in a selectivity for VIP binding and the subsequent receptor activation, a series of chimeric receptors between the VIP and PACAP receptors was constructed, expressed in COS-7 cells, and analyzed for ligand binding and cAMP generation [21].
• Since PACAP and follistatin are colocalized in multiple tissues including the brain, adrenals, and gonads, our findings may reflect a broadly distributed autocrine/paracrine mechanism for modification of activin effects that is under PACAP control [18].
• PACAP is expressed within the hypothalamus, and concentrations of PACAP are 2- to 4-fold higher in the portal circulation than in the general circulation [19].
• Pituitary adenylate cyclase activating polypeptide messenger RNA in the paraventricular nucleus and anterior pituitary during the rat estrous cycle [20].

Associations of Adcyap1 with chemical compounds

• The PACAP-stimulated BrdU uptake was inhibited (70%-80%) by inhibitors of adenosine 3',5'-cyclic monophosphate, phosphatidylinositol 3 kinase, and protein tyrosine kinase as well as mitogen-activated protein kinase [17].
• Diazoxide further increases the PACAP-activated current by 78% (P < 0.05; n = 6) [22].
• They secrete histamine and chromogranin A-derived peptides, such as pancreastatin, in response to gastrin and pituitary adenylate cyclase-activating peptide (PACAP) [23].
• Effects of vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) on the spontaneous release of acetylcholine from the rat hippocampus by brain microdialysis [24].
• The effect of PACAP on c-fos and c-jun expression in AR4-2J cells was rapid (20 min), transient (1-2 h), dose-dependent IC50, 0.5 nM) and was abolished by the specific PACAP receptor antagonist PACAP-(6-38)-peptide or inhibitors of protein kinase C or tyrosine kinases [25].

Physical interactions of Adcyap1

• This suggests that there is a nonbiologically relevant high affinity VIP-binding site within the rat PACAP receptor [21].
• Both PACAP (1-27)-peptide and PACAP-(1-38)-peptide strongly increased the DNA binding activity of the c-fos/ c-jun heterodimer transcription factor AP-1 at 10 nM and also stimulated AP-1 transcriptional activity up to 20-fold in AR4-2J cells [25].
• The TTF-1 homeodomain binds to six of the seven putative binding domains observed in the 5'-flanking region of the PACAP gene [3].
• Longitudinal muscle activity is regulated by excitatory VIP/PACAP/NOS interneurons coupled to cholinergic/tachykinin motor neurons innervating longitudinal muscle [26].
• We previously reported that PACAP coupled to the PAC1 receptor to evoke dihydropyridine-sensitive early (15 to 20 minutes) catecholamine secretion and cAMP response element binding protein-mediated trans-activation of the secretory protein chromogranin A promoter in PC12 pheochromocytoma cells [27].

Co-localisations of Adcyap1

• In some fibres, which seem to originate in the local paracervical ganglia, PACAP was co-localized with vasoactive intestinal polypeptide [28].
• 5. In the hypothalamus PACAP partially colocalizes with oxytocin- and tyrosine hydroxylase-immunoreactivities [29].

Regulatory relationships of Adcyap1

• Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) receptors are closely related G protein-coupled receptors with seven-transmembrane domains [21].
• Evidence that pituitary adenylate cyclase activating polypeptide suppresses follicle-stimulating hormone-beta messenger ribonucleic acid levels by stimulating follistatin gene transcription [18].
• Pituitary adenylate cyclase activating polypeptide (PACAP) inhibited dose dependently the DNA synthesis stimulated by arginine vasopressin (AVP) in cultured rat aortic smooth muscle cells (SMC) [30].
• Galanin inhibited BB- and PACAP-stimulated secretin release and production of second messengers in a concentration-dependent and pertussis toxin-sensitive manner [31].
• Pituitary adenylate cyclase-activating polypeptide stimulates cardiodilatin/atrial natriuretic peptide (CDD/ANP-(99-126) secretion from cultured neonatal rat myocardiocytes [32].

Other interactions of Adcyap1

• The cAMP responses of these receptors generally correlated with the ability of VIP to compete for PACAP radioligand binding with the exceptions for some particular chimeras [21].
• One of the actions of PACAP identified previously is to decrease FSHbeta messenger RNA (mRNA) levels [18].
• Pretreatment with nifedipine (10 microM), an L-type Ca2+ channel blocker, reduced PACAP-evoked pancreastatin secretion by 50-60%, gastrin-evoked secretion by approximately 80% and abolished the response to Bay K 8644 [23].
• Assignments of the genes for rat pituitary adenylate cyclase activating polypeptide (Adcyap1) and its receptor subtypes (Adcyap1r1, Adcyap1r2, and Adcyap1r3) [33].
• Furthermore, in alphaT3-1 cells PACAP activation of the follistatin promoter appears to be via the cAMP-dependent protein kinase A pathway [18].

Analytical, diagnostic and therapeutic context of Adcyap1

• In the present series of experiments we demonstrate that PACAP-induced suppression of FSHbeta mRNA correlates with a rise in follistatin mRNA levels in primary pituitary cell cultures [18].
• In the present study, we used in situ hybridization and real-time polymerase chain reaction to examine the expression of Pacap mRNA within the paraventricular nucleus (PVN) and anterior pituitary throughout the estrous cycle of the rat [20].
• PACAP action on D cells was measured by [Ca(2+)](i) and radioimmunoassay [1].
• Molecular cloning and tissue distribution of a receptor for pituitary adenylate cyclase-activating polypeptide [34].
• PACAP effects on ECL cells were analyzed by video imaging of [Ca(2+)](i) and histamine release; its effects on gastric glands were examined by confocal microscopy of [Ca(2+)](i) in ECL and parietal cells [1].

References