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The presence of the pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors PAC(1), VPAC(1), and VPAC(2) was studied in the lizard Podarcis sicula gastrointestinal and respiratory tissues. The expression and distribution of this neuropeptide was investigated using RT-PCR, immunohistochemistry, and in situ hybridization techniques. RT-PCR showed that several tissues of this reptile synthesize an mRNA encoding for PACAP. Performing in situ hybridization and immunohistochemistry, we found a wide distribution of PACAP and its mRNA in intestine, stomach, liver, and lung. PACAP receptors possess a specific distribution in both gastrointestinal and respiratory system. Further, we analyzed the conservation of PACAP amino acid sequence demonstrating that this peptide in the lizard is very similar to that of other vertebrates. Our findings suggest that also in reptiles an effective PACAP system is present and that it could be implicated in some essential physiological functions as a result of its high conservation amongst vertebrates.
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http://dx.doi.org/10.1007/s12031-009-9178-7 | DOI Listing |
Cephalalgia
September 2025
Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, USA.
Migraine is a complex neurological disorder involving multiple neuropeptides that modulate nociceptive and sensory pathways. The most studied peptide is calcitonin gene-related peptide (CGRP), which is a well-established migraine trigger and therapeutic target. Recently, another peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), has emerged as an alternative target for migraine therapeutics.
View Article and Find Full Text PDFSci Adv
September 2025
Laboratory of Neurobiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Acute sleep deprivation (SD) rapidly alleviates depression, addressing a critical gap in mood disorder treatment. Rapid eye movement SD (REM SD) modulates the excitability of vasoactive intestinal peptide (VIP) neurons, influencing the synaptic plasticity of pyramidal neurons. However, the precise mechanism remains undefined.
View Article and Find Full Text PDFBiochem Pharmacol
September 2025
Section on Molecular Neuroscience, NIMH-IRP, Bethesda, MD, USA. Electronic address:
The PACAP receptor PAC1 is a G-coupled family B1 GPCR for which the highest-affinity endogenous peptide ligands are the pituitary adenylate cyclase-activating peptides PACAP38 and PACAP27, and whose most abundant endogenous ligand is PACAP38. PACAP action at PAC1 is implicated in neuropsychiatric disorders, atherosclerosis, pain chronification, and protection from neurodegeneration and ischemia. As PACAP also interacts with two related receptors, VPAC1 and VPAC2, highly selective ligands, both agonists and antagonists, for PAC1 have been sought.
View Article and Find Full Text PDFBehav Neurosci
September 2025
University of Vermont, Department of Psychological Science.
Pituitary adenylate cyclase-activating polypeptide (PACAP, ) is a highly conserved neuropeptide that plays essential roles in numerous physiological functions, and central PACAP signaling has been associated with mechanisms regulating stress-induced psychopathologies. PACAP binds to several receptor subtypes, including PAC1 (), VPAC1 (), and VPAC2 (), to activate several signaling cascades that can alter neuronal excitability and enhance indices of neuroplasticity, and much of our prior work has suggested that the anxiogenic effects of bed nucleus of the stria terminalis (BNST) PACAP depend on the activation of PAC1 receptors. To complement our previous work that evaluated the roles of BNST PACAP expression and secretion in anxiety-related responses, we employed in the current work chemogenetic approaches in male PAC1-Ires-Cre mice to directly and specifically modulate the activities of BNST PAC1 receptor-expressing neurons.
View Article and Find Full Text PDFCephalalgia
August 2025
Department of Pharmacology and Toxicology, The University of Otago, Dunedin, New Zealand.
The neuropeptides pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) play roles in vasodilation, the immune response and neuronal signaling, with recent links to headache disorders. This association has resulted in considerable interest in targeting this family of peptides and their receptors for drug development, and, notably, an anti-PACAP antibody has reported clinical efficacy in reducing migraine frequency. The PACAP/VIP ligands act at G protein-coupled receptors (GPCRs).
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