Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MAPK and Akt pathways are predominant mediators of trophic signaling for many neuronal systems. Among the vasoactive intestinal peptide/secretin/glucagon family of related peptides, pituitary adenylate cyclase-activating polypeptide (PACAP) binding to specific PAC(1) receptor isoforms can engage multiple signaling pathways and promote neuroprotection through mechanisms that are not well understood. Using a primary sympathetic neuronal system, the current studies demonstrate that PACAP activation of PAC(1)HOP1 receptors engages both MAPK and Akt neurotrophic pathways in an integrated program to facilitate neuronal survival after growth factor withdrawal. PACAP not only stimulated prosurvival ERK1/2 and ERK5 activation but also abrogated SAPK/JNK and p38 MAPK signaling in parallel. In contrast to the potent and rapid effects of PACAP in ERK1/2 phosphorylation, PACAP stimulated Akt phosphorylation in a late phase of PAC(1)HOP1 receptor signaling. From inhibitor and immunoprecipitation analyses, the PACAP/PAC(1)HOP1 receptor-mediated Akt responses did not represent transactivation mechanisms but appeared to depend on G alpha(q)/phosphatidylinositol 3-kinase gamma activity and vesicular internalization pathways. Phosphatidylinositol 3-kinase gamma-selective inhibitors blocked PACAP-stimulated Akt phosphorylation in primary neuronal cultures and in PAC(1)HOP1-overexpressing cell lines; RNA interference-mediated knockdown of the receptor effectors attenuated PACAP-mediated Akt activation. Similarly, perturbation of endocytic pathways also blocked Akt phosphorylation. Between ERK and Akt pathways, PACAP-stimulated Akt signaling was the primary cascade that attenuated cultured neuron apoptosis after growth factor withdrawal. The partitioning of PACAP-mediated Akt signaling in endosomes may be a key mechanism contributing to the high spatial and temporal specificity in signal transduction necessary for survival pathways.
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PMID:Pituitary adenylate cyclase-activating polypeptide (PACAP)/PAC1HOP1 receptor activation coordinates multiple neurotrophic signaling pathways: Akt activation through phosphatidylinositol 3-kinase gamma and vesicle endocytosis for neuronal survival. 2009 65

The pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the glucagon-related family that occurs in two amidated forms with 38 (PACAP38) and 27 (PACAP27) amino acids. First discovered in the brain, it was then localized in several peripheral tissues of mammals, including the testis. However, current knowledge of the expression and function of PACAP and its receptor PAC(1) in the reproductive system of non-mammalian vertebrates, and particularly in the testis, is still limited. The aim of this work was to study the presence of PACAP and its receptor PAC(1) in the testis of two non-mammalian vertebrates during the breeding season: the crested newt Triturus carnifex and the wall lizard Podarcis sicula. The expression and distribution of this neuropeptide and its receptor PAC(1) were investigated by using in situ hybridization and immunohistochemistry techniques. Our results demonstrated that PACAP and its receptor PAC(1) were highly represented in the testis of these two species. In particular, we showed that they are present within some germ cells and that PACAP, unlike in mammals, is expressed also in the somatic cells (Sertoli and Leydig cells) of the testis of these two non-mammalian vertebrates, suggesting that this neuropeptide is involved in the hormonal control of spermatogenesis and steroidogenesis.
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PMID:Pituitary adenylate cyclase-activating polypeptide and its receptor PAC1 in the testis of Triturus carnifex and Podarcis sicula. 2033 77

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are members of a superfamily of structurally related peptide hormones that includes glucagon, glucagon-like peptides, secretin, gastric inhibitory peptide (GIP) and growth hormone-releasing hormone (GHRH). VIP and PACAP exert their actions through three GPCRs - PAC(1) , VPAC(1) and VPAC(2) - belonging to class B (also referred to as class II, or secretin receptor-like GPCRs). This family comprises receptors for all peptides structurally related to VIP and PACAP, and also receptors for parathyroid hormone, corticotropin-releasing factor, calcitonin and related peptides. PAC(1) receptors are selective for PACAP, whereas VPAC(1) and VPAC(2) respond to both VIP and PACAP with high affinity. VIP and PACAP play diverse and important roles in the CNS, with functions in the control of circadian rhythms, learning and memory, anxiety and responses to stress and brain injury. Recent genetic studies also implicate the VPAC(2) receptor in susceptibility to schizophrenia and the PAC(1) receptor in post-traumatic stress disorder. In the periphery, VIP and PACAP play important roles in the control of immunity and inflammation, the control of pancreatic insulin secretion, the release of catecholamines from the adrenal medulla and as co-transmitters in autonomic and sensory neurons. This article, written by members of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) subcommittee on receptors for VIP and PACAP, confirms the existing nomenclature for these receptors and reviews our current understanding of their structure, pharmacology and functions and their likely physiological roles in health and disease. More detailed information has been incorporated into newly revised pages in the IUPHAR database (http://www.iuphar-db.org/DATABASE/FamilyMenuForward?familyId=67).
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PMID:Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1. 2228 55

The pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the glucagon-related family and occurs in two amidated forms, PACAP38 and PACAP27, with 38 and 27 amino acids, respectively. PACAP acts by binding to three different receptors, that are classified by their binding affinity for PACAP and VIP (vasoactive intestinal polypeptide): PAC(1)R (PACAP-specific receptor) exclusively binds PACAP, while VPAC(1)R (VIP/PACAP receptor, subtype 1) and VPAC(2)R (VIP/PACAP receptor, subtype 2) bind both PACAP and VIP. PACAP, first discovered in the brain, was then localized in several peripheral tissues of mammals, including the ovary. Besides mammals, PACAP and its receptors have been reported in fish too; however, less is known about the presence of PACAP in the fish ovary and the studies are limited to teleosts. The aim of our work was to study the distribution of the PACAP/PACAP-Rs system in the ovary of the cartilaginous fish Torpedo marmorata. Using in situ hybridization (ISH) and immunohistochemistry techniques, we demonstrated that PACAP and its receptors are widely represented in the Torpedo ovary in a stage-dependent manner. Moreover, our findings suggest an involvement of this peptide in the whole follicologenesis, probably influencing steroidogenesis, follicle development, and oocyte growth.
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PMID:Cellular localization of PACAP and its receptors in the ovary of the spotted ray Torpedo marmorata Risso 1880 (Elasmobranchii: Torpediniformes). 2302 97

Pituitary adenylate cyclase activating polypeptide (PACAP) is a well-conserved neuropeptide characteristic of vertebrates. This pluripotent hypothalamic neuropeptide regulates neurotransmitter release, intestinal motility, metabolism, cell division/differentiation, and immunity. In vertebrates, PACAP has a specific receptor (PAC1) but it can also activate the Vasoactive Intestinal Peptide receptors (VPAC1 and VPAC2). The evolution of the vertebrate PACAP ligand - receptor pair has been well-described. In contrast, the situation in invertebrates is much less clear. The PACAP ligand - receptor pair in invertebrates has mainly been studied using heterologous antibodies raised against mammalian peptides. A few partial PACAP cDNA clones sharing >87% aa identity with vertebrate PACAP have been isolated from a cnidarian, several protostomes and tunicates but no gene has been reported. Moreover, current evolutionary models of the peptide and receptors using molecular data from phylogenetically distinct invertebrate species (mostly nematodes and arthropods) suggests the PACAP ligand and receptors are exclusive to vertebrate genomes. A basal deuterostome, the cephalochordate amphioxus (Branchiostoma floridae), is the only invertebrate in which elements of a PACAP-like system exists but the peptides and receptor share relatively low sequence conservation with the vertebrate homolog system and are a hybrid with the vertebrate glucagon system. In this study, the evolution of the PACAP system is revisited taking advantage of the burgeoning sequence data (genome and transcriptomes) available for invertebrates to uncover clues about when it first appeared. The results suggest that elements of the PACAP system are absent from protozoans, non-bilaterians, and protostomes and they only emerged after the protostome-deuterostome divergence. PACAP and its receptors appeared in vertebrate genomes and they probably shared a common ancestral origin with the cephalochordate PACAP/GCG-like system which after the genome tetraploidization events that preceded the vertebrate radiation generated the PACAP ligand and receptor pair and also the other members of the Secretin family peptides and their receptors.
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PMID:Tracing the Origins of the Pituitary Adenylate-Cyclase Activating Polypeptide (PACAP). 3301 83


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