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)

The effects of pituitary adenylate cyclase activating polypeptide (PACAP) and related peptides on phagocytosis of fluorescent latex beads by mouse peritoneal macrophages were examined using flow cytometry (FCM). PACAP38, PACAP27 and vasoactive intestinal peptide (VIP) enhanced phagocytosis in a dose-dependent manner. Relative potencies of related peptides at a concentration of 10(-6) M were PACAP38 > PACAP27 > VIP > secretin > glucagon > (peptide with NH2-terminal histidine and COOH-terminal methionine amide, in short PHM). PACAP(6-38) was as effective as PACAP38. PACAP(6-27) enhanced phagocytosis more effectively than did PACAP27. PACAP(28-38) slightly enhanced phagocytosis. The present result suggest that PACAP38 is one of the mediators that the nervous system uses to modulate the immune system.
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PMID:Enhancement of phagocytosis in mouse macrophages by pituitary adenylate cyclase activating polypeptide (PACAP) and related peptides. 855 21

During migration and for about 2 days after their arrival in the gonadal ridges, primordial germ cells (the embryonic precursors of gametes of the adult animal) proliferate actively. Certain growth factors, such as stem cell factor and leukemia inhibitory factor, seem to be essential for survival, proliferation and possibly differentiation of mouse primordial germ cell in vivo and/or in vitro. Similarly, increase in intracellular cAMP is followed by a marked enhancement of primordial germ cell proliferation, at least in culture. In the present study, we show that pituitary adenylate cyclase-activating polypeptides (PACAP-27 and PACAP-38), two neuropeptides of the secretin-glucagon-vasoactive intestinal polypeptide-GH-releasing hormone family, stimulate in vitro proliferation of mouse primordial germ cells, bind to primordial germ cells and gonadal somatic cells (possibly to type I PACAP receptor) and activate adenylate cyclase in the same cells. Moreover, PACAP-like immunoreactivity was found in gonadal ridges, mostly on germ cell surface. In conclusion, evidence is provided that PGC proliferation can be stimulated by certain bioactive polypeptides, thus suggesting a novel regulatory role for such compounds in early gonad development.
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PMID:Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates adenylate cyclase and promotes proliferation of mouse primordial germ cells. 856 32

1. The effects of pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP) and secretin on pancreatic endocrine secretions and vascular resistance were investigated and compared in the isolated perfused pancreas of the rat. The PACAP/VIP receptor types involved have been characterized. 2. On insulin secretion, in the range 10(-11) to 10(-8) M, PACAP and VIP elicited a concentration-dependent biphasic response from pancreas perfused with 8.3 mM glucose; the peptides were equipotent. In contrast, secretin was ineffective in the range 10(-11) to 10(-9) M; at 10(-8) and 10(-7) M, it induced only low and transient insulin responses. On the other hand, the peptides did not modify the basal insulin release in the presence of a non stimulating glucose concentration (2.8 mM). 3. On glucagon secretion, PACAP and VIP (10(-11) to 10(-8) M) but also secretin (10(-9) to 10(-7) M) caused a concentration-dependent peak shaped response from pancreas perfused with 2.8 mM glucose; PACAP and VIP were equipotent and 20 times more potent then secretin. On the other hand, the peptides did not affect the glucagon release in the presence of 8.3 mM glucose. 4. On pancreatic vessels, in the range 10(-11) to 10(-9) M, the three peptides were equipotent in inducing a concentration-dependent sustained increase in pancreatic flow rate. On the other hand, at the high concentration of 10(-7) M PACAP but not VIP provoked a transient decrease of flow rate. 5. This study provides evidence for PACAP/VIP type II receptors mediating insulin and glucagon secretion as well as vasodilatation in rat pancreas. In addition, the different efficacies of secretin suggest that these effects are mediated by different PACAP/VIP type II receptor subtypes.
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PMID:Comparative effects of PACAP and VIP on pancreatic endocrine secretions and vascular resistance in rat. 864 26

The two forms of pituitary adenylate cyclase-activating polypeptide, PACAP27 and PACAP38, are two neuropeptide hormones related to the vasoactive intestinal peptide/secretin/ glucagon family of peptides. PACAP receptors that are positively coupled to adenylyl cyclase and phospholipase C have been identified in cultured cerebellar granule cells. Using the reverse transcription-polymerase chain reaction methodology, we demonstrated the expression of the PACAP-R and PACAP-R-hop mRNAs in cultured granule cells. When grown in the absence of serum or in low K+ concentrations, these neurons underwent apoptosis, a naturally occurring process characterized by cell shrinkage and internucleosomal DNA cleavage. We used these models of programmed cell death to study the relationship between PACAP receptor activation and neuronal apoptosis. Treatment with PACAP27 and PACAP38 reduced the development of apoptosis in a dose-dependent manner. The neuroprotective activity of PACAP was mimicked by high concentrations of vasoactive intestinal peptide or forskolin but not by carbamylcholine. Thus, we suggest that the activation of type I PACAP receptors may contribute to the survival of cerebellar granule neurons.
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PMID:Pituitary adenylate cyclase activating polypeptide prevents apoptosis in cultured cerebellar granule neurons. 870 Jan 20

Pituitary adenylate cyclase-activating polypeptide (PACAP)-27 and PACAP-38 are neuropeptides of the vasoactive intestinal peptide/secretin/glucagon family. We previously described alternative splicing of the region encoding the third intracellular loop of the PACAP receptor generating six isoforms with differential signal transduction properties (Spengler, D., Waeber, C., Pantaloni, C., Holsboer, F., Bockaert, J., Seeburg, P. H., and Journot, L. (1993) Nature 365, 170-175). In addition, we demonstrated that the potencies of the two forms of PACAP are similar for adenylate cyclase stimulation, whereas PACAP-38 is more potent than PACAP-27 in phospholipase C activation. In the present work, we document the existence of a new splice variant of the PACAP receptor that was characterized by a 21-amino-acid deletion in the N-terminal extracellular domain. We demonstrate that this domain modulates receptor selectivity with respect to PACAP-27 and -38 binding and controls the relative potencies of the two agonists in phospholipase C stimulation.
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PMID:Alternative splicing in the N-terminal extracellular domain of the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor modulates receptor selectivity and relative potencies of PACAP-27 and PACAP-38 in phospholipase C activation. 870 26

The two forms of pituitary adenylate cyclase-activating polypeptide, PACAP27,and PACAP38, are novel members of the vasoactive intestinal peptide (VIP)/secretin/glucagon family of peptides. PACAP receptors that are positively coupled to adenylate cyclase and phospholipase C have been recently identified. We examined the expression of PACAP receptors in the rat cortex, hippocampus, cerebellum and hypothalamus during postnatal development. Functional studies revealed PACAP stimulation of cAMP formation in all the brain areas examined and [3H]inositol monophosphate ([3H]InsP) accumulation only in the cerebellum and hypothalamus. Throughout development, the efficacy or PACAP in stimulating cAMP formation slightly increased in the cortex and hypothalamus and decreased in the hippocampus and cerebellum; PACAP stimulation of [3H]InsP formation decreased in the cerebellum and remained steady in the hypothalamus. The effects of PACAP27 and PACAP38 on cAMP levels and inositol phospholipid hydrolysis were dose-dependent between 1 and 100 nM. In the same brain areas, treatment with VIP increased cAMP formation at doses greater than 100nM and failed to affect [3H]InsP content, thus suggesting the existence of type-1 PACAP receptors. The reverse transcription polymerase chain reaction (RT-PCR) was used to analyse the mRNA expression of type-1 PACAP receptor splice variants. PACAP receptor gene expression in the central nervous system was regulated in a developmental- and tissue-specific manner. The PACAP-R transcript was detected in all the brain areas examined whereas PACAP-R-hop mRNA ocurred only in the cerebellum and hypothalamus. The different expression profiles and functional properties of PACAP receptors in the developing rat brain suggest an involvement of PACAP in histogenesis, maturation and neurotransmission.
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PMID:Tissue-specific and developmental expression of pituitary adenylate cyclase-activating polypeptide (PACAP) receptors in rat brain. 871 2

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the secretin/glucagon/vasoactive intestinal peptide (VIP)/growth hormone releasing hormone (GHRH) family of neuropeptides, several of which stimulate steroidogenesis in ovarian granulosa cells. PACAP receptors are of two major subtypes; the type I receptor (PACAP-I-R) has much higher affinity for PACAP than VIP, and the type II receptor (PACAP-II-R) has similar affinity for both peptides. In the rat ovary, expression of the PACAP gene was demonstrated by amplification of ovarian RNA by the reverse transcription/polymerase chain reaction (RT-PCR). In addition, hybridization of Northern blots of rat ovarian poly(A)+ RNA with a 706-nt rat hypothalamic PACAP-I-R cDNA probe revealed the presence of a 7.0 kb PACAP receptor transcript, similar to that detected in brain and hypothalamus. RT-PCR using specific primers for the PACAP-I-R gene yielded products of the expected size with RNA obtained from ovarian tissue, brain, and hypothalamus. The authenticity of the PCR products was confirmed by Southern blotting and nested PCR, which revealed at least three splice variants of the PACAP-I-R in the rat ovary. These findings demonstrate that both PACAP and PACAP-I-R isoforms are expressed in the rat ovary, where they could exert autocrine or paracrine actions on granulosa cell function.
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PMID:Expression of PACAP and its type-I receptor isoforms in the rat ovary. 873 84

Cytochemical analysis demonstrated that a high percentage of human Y-79 retinoblastoma cells displayed a specific labeling by the biotinyl derivative of pituitary adenylate cyclase-activating polypeptide (PACAP), a novel neuropeptide of the secretin-vasoactive intestinal peptide (VIP) family of peptides. In cell membranes, the two molecular forms of PACAP, the one with 38 (PACAP 38) and the other with 27 (PACAP 27) amino acids, displaced the binding of 125I-PACAP 27 with IC50 values in the picomolar range and increased adenylyl cyclase activity by 100-fold with EC50 values of 27 and 180 pM, respectively. VIP, human peptide histidine-isoleucine, glucagon, and secretin were much less effective and potent in both receptor assays. The PACAP receptor antagonists PACAP 6-27 and PACAP 6-38 and an antiserum directed against the stimulatory G protein Gs inhibited the PACAP stimulation of adenylyl cyclase. 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. However, this effect was not antagonized by either PACAP 6-38 or PACAP 6-27. 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.
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PMID:Presence of pituitary adenylate cyclase-activating polypeptide receptors in Y-79 human retinoblastoma cells. 875 38

The dorsal vagal complex (DVC) and nucleus raphe obscurus (nROb) are currently known to control vagal outflow to the stomach and the pancreas. Elucidation of neurotransmitters in these nuclei that control vagal outflow has become necessary to determine the endogenous circuitry for control of gastric motor activity and pancreatic hormone secretion. In this review, the author's data on the effects of selected peptides on intragastric pressure and gastric contractility as well as on pancreatic glucagon and insulin secretion in the DVC and nROb are presented. Microinjection of thyrotropin-releasing hormone (TRH) or pituitary adenylate cyclase-activating polypeptide (PACAP38) into the nROb results in gastric excitatory motor responses, whereas substance P (SP) and vasoactive intestinal polypeptide (VIP) evoke gastric relaxation. Irrespective of colocalization of TRH and SP in the serotonergic neurons of the nROb, these peptides independently affect gastric motor function when microinjected into the nROb. The inhibitory effect of SP on gastric motor function in the nROb is apparently mediated via nitric oxide in the DVC and involves peripheral VIP, acetylcholine, gamma-aminobutyric acid and nitric oxide. Microinjection of endothelin, PACAP38, and VIP into the DVC evokes increases in gastric motor activity. Pancreatic polypeptide, microinjected into the DVC, does not affect basal plasma insulin and glucagon concentration but potentiates glucose-stimulated insulin secretion. All these data make an important contribution to our understanding of the vagal mechanisms controlling gastric motor and endocrine pancreatic function.
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PMID:Role of selected peptides in the vagal regulation of gastric motor and endocrine pancreatic function. 887 96

Pituitary adenylate cyclase-activating polypeptides (PACAP-27 and PACAP-38) are neuropeptides of the vasoactive intestinal polypeptide (VIP)/secretin/glucagon family. PACAP receptors are expressed in different brain regions, including cerebellum. We used primary culture of rat cerebellar granule neurons to study the effect of PACAP-38 on apoptosis induced by potassium deprivation. We demonstrated that PACAP-38 increased survival of cerebellar neurons in a dose-dependent manner by decreasing the extent of apoptosis estimated by DNA fragmentation. PACAP-38 induced activation of the extracellular signal-regulated kinase (ERK)-type of mitogen-activated protein (MAP) kinase through a cAMP-dependent pathway. PD98059, an inhibitor of MEK (MAP kinase kinase), completely abolished the antiapoptotic effect of PACAP-38, suggesting that MAP kinase pathway activation is necessary for PACAP-38 action.
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PMID:Pituitary adenylate cyclase-activating polypeptide (PACAP-38) protects cerebellar granule neurons from apoptosis by activating the mitogen-activated protein kinase (MAP kinase) pathway. 898 38


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