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 two forms of pituitary adenylate cyclase-activating polypeptide (PACAP), PACAP27 and PACAP38, are 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 recently identified. We have investigated the expression of PACAP-Rs in undifferentiated and differentiated PC-12 cells. PACAP27 and PACAP38 failed to significantly increase cAMP or [3H]inositol monophosphate levels in undifferentiated PC-12 cells treated with vehicle, insulin-like growth factor I, or epidermal growth factor but greatly elevated levels after differentiation with nerve growth factor (NGF) or basic fibroblast growth factor. PACAP responsiveness increased significantly after 24 hr of NGF treatment, reaching a maximum within 4 days. At this time of differentiation, the effect of PACAP was dose dependent between 1 nM and 0.1 microM, whereas vasoactive intestinal peptide, at the maximal dose of 10 microM, slightly increased cAMP formation and failed to affect [3H]inositol monophosphate content. Radioreceptor assays, performed with 125I-PACAP27, revealed the induction of high affinity type I PACAP receptors in differentiated PC-12 cells. Using reverse transcription-polymerase chain reaction methodology, we showed the absence of type I PACAP receptor mRNAs in undifferentiated PC-12 cells and the expression of PACAP-R-hop mRNA after NGF or basic fibroblast growth factor treatment. The increased PACAP responsiveness induced by these growth factors in PC-12 cells may therefore result from the expression of the PACAP-R-hop isoform, positively coupled to both adenylyl cyclase and phospholipase C.
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PMID:Differentiation induces pituitary adenylate cyclase-activating polypeptide receptor expression in PC-12 cells. 762 75

Pituitary adenylate cyclase activating polypeptide (PACAP) is a new member of the secretin/glucagon/vasoactive intestinal peptide (VIP) family. It stimulates adenylate cyclase in cultured rat pituitary cells, which have PACAP-specific receptors and expression of pituitary hormones. Therefore, PACAP is considered as a hypophysiotropic hormone. If so, there might be a feedback regulatory mechanism between pituitary hormones and hypothalamic PACAP. In the present study, we used nuclear run-on and RNase protection assays to examine whether transcription of the PACAP gene in the rat hypothalamus would change after hypophysectomy. PACAP levels in the hypothalamus were also determined by radioimmunoassay. The transcriptional rate of the PACAP gene and PACAP mRNA content decreased 1 and 2 weeks after hypophysectomy. Radioimmunoassayable PACAP levels in the hypothalamus also decreased after hypophysectomy. These findings suggest that the reduced rate of PACAP gene transcription after hypophysectomy causes the decreased mRNA and peptide levels in the hypothalamus. Replacement with GH, PRL, T4, corticosterone, and testosterone significantly restored PACAP mRNA levels in hypophysectomized rats to those in control animals. The results suggest that feedback regulation takes place between pituitary hormones or pituitary-dependent factors and hypothalamic PACAP.
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PMID:Effect of hypophysectomy on pituitary adenylate cyclase activating polypeptide gene expression in the rat hypothalamus. 765 92

Two types of cDNA encoding PACAP receptors were isolated from the rat brain cDNA library by homology screening with a cDNA probe for VIP receptor. Nucleotide sequence analysis indicated that these two types of receptor mRNA were generated by alternative splicing mechanisms. These two cloned cDNAs were introduced into CHO cells respectively. Resultant transformants showed specific binding to [125I]PACAP27 which was displaced by unlabeled PACAP27 but not by VIP. Thus, these receptors are two subtypes of Type I PACAP receptor (Type I-A and Type I-B). The amino acid sequences of rat PACAP receptors deduced by the cDNAs showed a remarkable similarity with rat receptors for VIP, secretin, glucagon, and GHRH. A 6.5 kb significant hybridizing signal of the PACAP receptor mRNA was detected in the rat brain, and slight signal was also detected in the lung and the liver.
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PMID:Molecular cloning and functional expression of rat cDNAs encoding the receptor for pituitary adenylate cyclase activating polypeptide (PACAP). 768 25

A receptor capable of recognizing VIP-related peptides with unusual functional characteristics and selectivity profile was characterized on human IGR37 melanoma cells. When using either [125I]VIP or [125I]N-AcPACAP27 as a tracer, PACAP38 had the highest affinity, while PACAP27, VIP, helodermin, GRF and the VIP fragment VIP10-28 showed the same low affinity. Moreover, this receptor did not recognize PHM, PHV, helospectin, secretin, GIP, glucagon and glucagon-like peptide-1(7-36). Surprisingly, none of the peptides significantly stimulated the cAMP production. By covalent crosslinking, the receptor was shown to have a M(r) = 60,500.
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PMID:A receptor for VIP-related peptides with an unusual selectivity profile on the melanoma cell line IGR37. 770 17

The signaling pathways whereby glucose and hormonal secretagogues regulate insulin-secretory function, gene transcription, and proliferation of pancreatic beta-cells are not well defined. We show that in the glucose-responsive beta-cell line INS-1, major secretagogue-stimulated signaling pathways converge to activate 44-kDa mitogen-activated protein (MAP) kinase. Thus, glucose-induced insulin secretion was found to be associated with a small stimulatory effect on 44-kDa MAP kinase, which was synergistically enhanced by increased levels of intracellular cAMP and by the hormonal secretagogues glucagon-like peptide-1 and pituitary adenylate cyclase-activating polypeptide. Activation of 44-kDa MAP kinase by glucose was dependent on Ca2+ influx and may in part be mediated by MEK-1, a MAP kinase kinase. Stimulation of Ca2+ influx by KCl was in itself sufficient to activate 44-kDa MAP kinase and MEK-1. Phorbol ester, an activator of protein kinase C, stimulated 44-kDa MAP kinase by both Ca(2+)-dependent and -independent pathways. Nerve growth factor, independently of changes in cytosolic Ca2+, efficiently stimulated 44-kDa MAP kinase without causing insulin release, indicating that activation of this kinase is not sufficient for secretion. In the presence of glucose, however, nerve growth factor potentiated insulin secretion. In INS-1 cells, activation of 44-kDa MAP kinase was partially correlated with the induction of early response genes junB, nur77, and zif268 but not with stimulation of DNA synthesis. Our findings suggest a role of 44-kDa MAP kinase in mediating some of the pleiotropic actions of secretagogues on the pancreatic beta-cell.
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PMID:Glucose, other secretagogues, and nerve growth factor stimulate mitogen-activated protein kinase in the insulin-secreting beta-cell line, INS-1. 771 82

The effects of PACAP on hepatic glucose metabolism were examined using the flow-through perfusion method for fed rat livers, because some of the glucagon superfamily peptides stimulate hepatic glucose output. Glucose output was significantly stimulated in a dose-dependent manner by more than 1 nM PACAP-27. The potency of its stimulation was equal to that of PACAP-38, greater than that of VIP, and clearly lower than that of glucagon. The cAMP output was also increased significantly by more than 1 nM PACAP-27; however, the degree and profile of cAMP output were not in parallel with those of glucose. Theophylline did not affect these stimulatory effects. On the other hand, in the perfusion experiment with Ca2+ free perfusate, the degrees of increase in glucose output induced by 15 and 40 nM PACAP-27 were significantly reduced. In conclusion, PACAP stimulates glucose output from the perfused rat liver, and Ca2+ rather than cAMP plays an important role in this action as a second messenger.
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PMID:PACAP stimulates glucose output from the perfused rat liver. 771 74

The gut-brain neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) is a novel highly conserved member of the secretin-glucagon-VIP peptide family comprising 38 or 27 amino acid residues. In this study, we investigate the actions of PACAP 1-27 or PACAP 1-38 on jejunal and caecal muscle strips from pig or guinea pig and demonstrate the neutralizing effect of two PACAP-specific monoclonal antibodies of the IgG1 subtype, RSP27II and RSP38. These antibodies were used to set up assay systems specific for PACAP 1-27 or PACAP 1-38. Monoclonal antibody RSP27II recognizes exclusively PACAP 1-27, whereas RSP38 binds only PACAP 1-38. PACAP 1-27 and PACAP 1-38 relax taenia caeci dose-dependently in the presence of guanethidine and scopolamine. Both peptides inhibit the spontaneous contractions of porcine jejunal muscle strips equipotently. Monoclonal antibodies RSP27II and RSP38 specifically neutralize the actions of either exogenously applied or endogenously released PACAP. Thus, they represent processing-specific tools to examine the physiological role of both molecular forms of PACAP in the gastrointestinal tract.
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PMID:Specific monoclonal antibodies neutralize the action of PACAP 1-27 or PACAP 1-38 on intestinal muscle strips in vitro. 772 28

Pituitary adenylate cyclase activating polypeptide (PACAP) isolated from ovine hypothalamus is considered to be a member of the vasoactive intestinal peptide/glucagon/secretin/growth hormone-releasing hormone family of peptides. Two forms of PACAP, PACAP38 and PACAP27, have been demonstrated in the rat hypothalamus. The PACAP precursor contains another peptide called PACAP-related peptide (PRP), but so far no information on this peptide in tissue exists. We have developed three radioimmunoassays specific for PACAP38, PACAP27 and PRP and demonstrate that all three preproPACAP peptides are expressed in the rat hypothalamus, the PACAP38/PACAP27 ratio being around 60 and the PACAP38/PRP ratio being around 10. HPLC analysis of hypothalamic extract showed that PACAP38 and PACAP27 are found in only one form corresponding to the respective synthetic peptides, whereas PRP eluted in two peaks, the predominant form corresponding to synthetic PRP1-29. The cellular distribution of PACAP38, PACAP27, and PRP and corresponding mRNA in the hypothalamus was determined with immunohistochemistry and in situ hybridization histochemistry. PACAP- and PRP-immunoreactive neuronal perikarya were observed in the medial parvocellular part of the paraventricular nucleus (PVN) in colchicine pretreated rats. Some cell bodies of magnocellular variety were found in the PVN. PACAP mRNA containing cells were observed in moderate numbers in the same parts of the paraventricular nucleus. PACAP- and PRP immunoreactive fibres and varicosities were distributed in the PVN and in the periventricular nucleus. These data show that PACAP38, PACAP27 and PRP are expressed in the parvocellular part of the PVN, implying roles as hypothalamic regulatory peptides.
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PMID:Gene expression of pituitary adenylate cyclase activating polypeptide (PACAP) in the rat hypothalamus. 775 1

Helospectin and pituitary adenylate cyclase activating polypeptide (PACAP), both recently isolated from the poisonous saliva of the American lizard or from ovine hypothalamus respectively, belong to the same peptide family as vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM) and glucagon. In the present study, occurrence and distribution patterns of nerve fibers containing helospectin- and PACAP-like immunoreactivity in the human vagina were investigated by immunohistochemistry. Double immunofluorescent labeling showed that helospectin or PACAP are co-expressed with VIP and PHM within subpopulations of VIP-immunoreactive nerve fibers. Nervous structures containing helospectin and VIP were particularly numerous in the internal mucous lining of the vagina and in free epithelial nerve endings, and an abundant network of nerve fibers surrounding blood vessels was detected. Nerve fibers co-expressing PACAP and VIP were more numerous than those expressing helospectin and VIP and were mainly found in close association with blood vessels as well as beneath and within the epithelium. Due to the lack of non-rabbit helospectin or PACAP antibodies, possible co-localizations between these two peptides could not be investigated at this time. The localizations demonstrated suggest possible roles of the two peptides in the regulation of local blood flow and lubrication of the vagina.
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PMID:Helospectin and pituitary adenylate cyclase activating polypeptide in the human vagina. 776 27

We report here that pituitary adenylate cyclase activating polypeptide (PACAP38), a new 38-residue neuropeptide of the secretin/glucagon family, is a potent inhibitor of calmodulin in vitro in the activation of bovine brain calmodulin-dependent cyclic nucleotide phosphodiesterase. The concentration of PACAP38 for half-maximal inhibition of the phosphodiesterase is 15 nM, one of the lowest for known calmodulin inhibitors. In the presence of Ca2+, PACAP38 binds strongly to calmodulin in a 1:1 ratio with a dissociation constant of about 28 nM. The binding is not dissociated by 4 M urea. In the absence of Ca2+ the binding is at random and can be dissociated by 4 M urea. Studies with PACAP38 derivatives show that the carboxyl half of the PACAP38 molecule is essential for the inhibition of calmodulin.
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PMID:Pituitary adenylate cyclase activating polypeptide is a potent calmodulin inhibitor. 788 41


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