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) on plasma insulin, glucagon, catecholamine, cortisol, glucose, triglyceride (TG), free fatty acid (FFA), cholesterol, and cyclic adenosine monophosphate (cAMP) concentrations were examined in unanesthetized normal dogs. A bolus injection of 6 pmol/kg PACAP27 elicited a transient increase in plasma insulin, epinephrine, and norepinephrine concentrations, with a peak value at 2 minutes after injection. Injections of 60 and 600 pmol/kg caused greater increases in these hormone concentrations in a dose-dependent manner. The plasma cortisol concentration was not changed by a bolus injection of 6 pmol/kg PACAP27, and was gradually increased by injections of 60 and 600 pmol/kg. Significant increases were observed from 10 and 5 minutes after the injection of 60 and 600 pmol/kg, respectively. The plasma glucagon concentration was not changed by either 6, 60, or 600 pmol/kg. The plasma glucose concentration decreased with 60 pmol/kg PACAP27 and increased with 600 pmol/kg. The plasma FFA concentration was increased gradually, with a peak value at 10 minutes after the injection, in a dose-dependent manner. The plasma TG concentration was slightly increased with 600 pmol/kg with a peak value at 10 minutes, although plasma cholesterol did not change. The plasma cAMP concentration increased significantly with 600 pmol/kg PACAP27, but not with 6 or 60 pmol/kg. These effects of PACAP27 were observed with a bolus injection of PACAP38 of an equal potency. Infusion of graded doses of PACAP27 (1, 3, and 10 pmol/kg/min every 20 minutes) caused a gradual increase in plasma cortisol, catecholamine, FFA, and cAMP concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pituitary adenylate cyclase-activating polypeptide: effects on pancreatic-adrenal hormone secretion and glucose-lipid metabolism in normal conscious dogs. 820 64

Insect diuretic hormones and their receptors regulate fluid and ion secretion and thus are attractive targets for the design of novel insect control agents. A complementary DNA clone encoding a corticotropin-releasing factor-related diuretic hormone receptor from the tobacco hornworm Manduca sexta was isolated by expression cloning in COS-7 cells. The receptor consists of 395 amino acids and contains seven putative transmembrane domains. The expressed receptor binds M. sexta diuretic hormone, as well as several related insect diuretic peptides with high affinity. Furthermore, each of these peptides stimulate adenylate cyclase in COS-7 cells transfected with the receptor. The M. sexta diuretic hormone receptor is homologous to the receptors for calcitonin, secretin, vasoactive intestinal peptide, parathyroid hormone, glucagon-like peptide 1, growth hormone-releasing hormone, pituitary adenylate cyclase-activating polypeptide, and glucagon. The M. sexta diuretic hormone receptor is the first nonmammalian member of this family to be identified.
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PMID:Expression cloning of an insect diuretic hormone receptor. A member of the calcitonin/secretin receptor family. 827 84

A cDNA that codes for two peptides in the glucagon superfamily has been isolated from sockeye salmon brain. The first peptide is related to growth hormone-releasing hormone (GHRH), which has high sequence similarity with PACAP-related peptide. The second peptide is structurally related to vasoactive intestinal peptide, which is also related to a newly identified peptide in mannals, pituitary adenylate-cyclase-activating polypeptide (PACAP). The salmon precursor contains 173 amino acids and has dibasic and monobasic enzyme-processing sites for cleavage of a 45-amino-acid GHRH-like peptide with a free C-terminus and a 38-amino-acid PACAP with an amidated C-terminus. The salmon GHRH-like peptide has 40% amino acid sequence identity with a human GHRH and 56% identity with human PACAP-related peptide. The 38-amino-acid salmon PACAP is highly conserved (89-92% identity) with only three or four amino acid substitutions compared with the human, ovine and rat 38-amino-acid PACAP. Not previously reported for mammalian species, a short precursor coding for only one peptide exists in salmon in addition to the long precursor coding for two peptides. In the short precursor, the coding region for GHRH is deleted leaving the PACAP-coding region in a correct reading frame. This provides one possible control mechanism for an increased expression of one peptide (PACAP) without the concomitant increase in the other peptide (GHRH) as occurs in a double-peptide precursor. The importance of the 3' non-translated region of the salmon GHRH/PACAP precursor in the regulation of translation is suggested by its 70% nucleotide sequence identity to the 3' non-translated regions of the mammalian PACAP precursors. The structural organization of the salmon GHRH/PACAP precursor provides a possible evolutionary scheme for precursors that contain tandem peptides in the glucagon superfamily.
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PMID:Two salmon neuropeptides encoded by one brain cDNA are structurally related to members of the glucagon superfamily. 834 11

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38 amino-acid peptide which belongs to the glucagon/secretin/vasoactive intestinal peptide superfamily. The sequence of PACAP is identical in all mammalian species studied so far but frog PACAP differs by one amino-acid from mammalian PACAP. The aim of the present study was to investigate the presence of PACAP in the hypothalamo-pituitary complex of the frog Rana ribibunda and to determine the biological activity of frog PACAP on homologous pituitary cells. The distribution of PACAP-containing neurons and fibers was examined by the indirect immunofluorescence method using an antiserum raised against the N-terminal region of the peptide. In the hypothalamus, PACAP-immunoreactive perikarya were localized in the preoptic nucleus and the dorsal and ventral infundibular nuclei. Beaded nerve fibers were observed coursing from the ventral infundibular nucleus to the external vascular layer of the median eminence. A dense network of immunoreactive axons terminated in the vicinity of the capillaries of the hypophysial portal system. The neurointermediate lobe and the distal lobe of the pituitary were devoid of immunoreactive elements. The amount of PACAP-like immunoreactive material in hypothalamus extracts was measured by radioimmunoassay; the apparent concentration of PACAP was 4.5 ng/mg protein. Synthetic frog PACAP38 and PACAP27 induced a similar dose-dependent stimulation of cAMP production in isolated frog distal lobe pituitary fragments (ED50 = 2 x 10(-8) M). At the maximum dose tested (5 x 10(-6) M), both frog PACAP38 and PACAP27 produced a 4-fold increase in cAMP production.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuroanatomical and physiological evidence for the involvement of pituitary adenylate cyclase-activating polypeptide in the regulation of the distal lobe of the frog pituitary. 839 65

Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide belonging to the vasoactive intestinal peptide (VIP)/secretion/glucagon family of peptides, interacts with a distinct high-affinity receptor (type I receptor) on a number of tissues. These PACAP type I receptors have a high affinity for PACAP and a low affinity for VIP and are present in the hypothalamus and anterior pituitary, where they regulate the release of adrenocorticotropin, luteinizing hormone, growth hormone, and prolactin, and in the adrenal medulla, where they regulate the release of epinephrine. Type I PACAP receptors are also present in high concentrations in testicular germ cells, where they may regulate spermatogenesis, and some transformed cell lines, such as the rat pancreatic acinar carcinoma cell AR4-2J. Here we report the molecular cloning and functional expression of the PACAP type I receptor isolated from an AR4-2J cell cDNA library by cross-hybridization screening with a rat VIP receptor cDNA. The cDNA sequence encodes a unique 495-amino acid protein with seven transmembrane domains characteristic of guanine nucleotide-binding regulatory protein-coupled receptors. A high degree of sequence homology with the VIP, secretin, glucagon-like peptide 1, parathyroid, and calcitonin receptors suggests its membership in this subfamily of Gs-coupled receptors. Results of binding studies and stimulation of cellular cAMP accumulation in COS-7 cells transfected with this cDNA are characteristic of a PACAP type I receptor. Cloning of the PACAP type I receptor will enhance our understanding of its distribution, structure, and functional properties and ultimately increase our understanding of its physiological role.
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PMID:Molecular cloning and functional expression of the pituitary adenylate cyclase-activating polypeptide type I receptor. 839 97

The binding of ovine pituitary adenylate cyclase-activating peptide (PACAP-38) to rat lung membranes was investigated using [125I]PACAP-38 as radioligand. Binding was rapid at 37 degrees C, reversible, saturable, and time, concentration, and temperature dependent. Kinetic parameters derived from saturation experiments revealed a Kd = 100 +/- 15 pM, Bmax = 310 +/- 36 fmol/mg protein, and a Hill slope factor (nH) of 1.17 +/- 0.12. Various chemically synthesized analogues of PACAP-38, as well as related peptides, were tested for their ability to displace [125I]PACAP-38. Of those that had an IC50 < 0.2 microM, the following order of potency was determined: PACAP-38 (IC50 = 25 nM) > or = [Ile2]PACAP-38 (IC50 = 31 nM) > PACAP-27 (IC50 = 54 nM) > [Tyr1]PACAP-38 (IC50 = 104 nM) > GHRH(1-29)NH2 (IC50 = 108 nM) > PHI (IC50 = 181 nM) > [Ser2]PACAP(2-38) (IC50 = 198 nM). Glucagon, PHM, secretin, and GIP exhibited little affinity in the same binding assay. Vasoactive intestinal peptide (VIP) had an IC50 in excess of 1 microM. When [125I]VIP was used as radioligand, PACAP-27 had an IC50 = 0.2 nM > PACAP-38 (IC50 = 0.5 nM) > VIP (IC50 = 16 nM). A novel analog of PACAP-38, [4-Cl-D-Phe6,Leu17]PACAP-38, was able to displace [125I]VIP very efficiently (IC50 = 1 nM), but had little potency in displacing [125I]PACAP-38 (IC50 = 320 nM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction of ovine pituitary adenylate cyclase-activating peptide (PACAP-38) with rat lung membranes. 839 24

Pituitary adenylate cyclase-activating polypeptide (PA-CAP) is a polypeptide hormone related to vasoactive intestinal polypeptide (VIP). Rat PACAP receptor cDNA was isolated from a brain cDNA library by cross-hybridization with rat VIP receptor cDNA. The recombinant PACAP receptor expressed in COS cells bound PACAP with about 1000 times higher affinity than VIP, and PACAP stimulated adenylate cyclase through the cloned PACAP receptor. The rat PACAP receptor consists of 495 amino acids, contains seven transmembrane segments, and has a significant similarity with other Gs-coupled receptors, such as VIP, glucagon, and secretin receptors. PACAP receptor mRNA was abundantly expressed in the brain, but not in the peripheral tissues except for the adrenal gland. In situ hybridization revealed a high level of expression of PACAP receptor mRNA in the hippocampal dentate gyrus, olfactory bulb, and cerebellar cortex.
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PMID:Molecular cloning and tissue distribution of a receptor for pituitary adenylate cyclase-activating polypeptide. 839 23

The two forms of pituitary adenylyl cyclase-activating polypeptide (PACAP-27 and -38) are neuropeptides of the secretin/glucagon/vasoactive intestinal polypeptide/growth-hormone-releasing hormone family and regulate hormone release from the pituitary and adrenal gland. They may also be involved in spermatogenesis, and PACAP-38 potently stimulates neuritogenesis and survival of cultured rat sympathetic neuroblast and promotes neurite outgrowth of PC-12 cells. The PACAP type-I receptor (found in hypothalamus, brain stem, pituitary, adrenal gland and testes), specific for PACAP, is positively coupled to adenylyl cyclase and phospholipase C. The recently cloned type II receptor does not discriminate between PACAP and vasoactive intestinal polypeptide and is coupled to only adenylyl cyclase. 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. On transfection of this cDNA, both PACAP-27 and -38 stimulate adenylyl cyclase with similar EC50 values (50% effective concentration, 0.1-0.4 nM), whereas only PACAP-38 stimulates phospholipase C with high potency (EC50 = 15 nM). Four other splice variants were isolated with insertions at the C-terminal end of the third intracellular loop. Expression of these cDNAs revealed altered patterns of adenylyl cyclase and phospholipase C stimulation, suggesting a novel mechanism for fine tuning of signal transduction.
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PMID:Differential signal transduction by five splice variants of the PACAP receptor. 839 27

The solution structures of the recently discovered neuropeptides PACAP38 and PACAP27 have been investigated in aqueous solution containing varying amounts of trifluoroethanol (TFE) by circular dichroism (CD) spectroscopy and a combination of 2D 1H nuclear magnetic resonance (NMR) spectroscopy, distance geometry, and refined molecular dynamics and energy minimization calculations. In aqueous solution both peptides show only small transitory amounts of stable structure while in 50% TFE they adopt ordered structures. Qualitative NOE data and the use of the chemical shift index of the alpha-protons identified the positions of alpha-helical regions. A set of low-energy conformations compatible with the quantitative NOE data were obtained for both and each set were subjected to RMS analysis to determine the positions of the secondary structure elements. PACAP38 has an initial disordered N-terminal domain of eight amino acids, followed by an alpha-helical structure stretching from Ser-9 to Val-26, which contains a discontinuity between Lys-20 and Lys-21, and in the C-terminal region there is a short alpha-helix between Gly-28 and Arg-34. The structure of PACAP27 mirrors remarkably closely that of PACAP38 and shows no fraying of the C-terminal helix. The physiological significance of the three structural domains (1-8, 9-26, and 27-38) of PACAP38 is shown by a comprehensive review of recent in vitro and in vivo investigations of PACAP analogues. The correspondence of the global structural features of PACAP with other members of this family of peptides (namely, secretin, glucagon, GHRF1-29 and VIP) is demonstrated by inspection of the chemical shift indices of the alpha-protons.
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PMID:Solution structure of pituitary adenylate cyclase activating polypeptide by nuclear magnetic resonance spectroscopy. 850 3

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the secretin/glucagon/vasoactive intestinal peptide (VIP) family. Our immunohistochemical and in situ hybridization histochemical studies indicated that PACAP-like immunoreactivity (PACAP-LI) and its mRNA were present in the germ cells in the rat testis. Because the testicular function is regulated by the pituitary gonadotropins, effect of hypophysectomy on the PACAP gene expression was investigated in the rat testis as an attempt to reveal the regulation of the testicular PACAP by the pituitary. The levels of testicular PACAP mRNA, which were determined by RNase protection assay, increased 2 weeks after hypophysectomy. In contrast, the levels of radioimmunoassayable PACAP decreased 2 weeks after the surgery. Immunohistochemistry showed that hypophysectomy did not change the distribution of PACAP-LI, although the number of immunopositive cells was markedly reduced after hypophysectomy. The replacement treatments of hypophysectomized animals with FSH or LH+FSH restored testicular PACAP mRNA to the levels in the control animals. On the other hand, all of these treatments (testosterone, LH, FSH, or LH+FSH) significantly increased radioimmunoassayable PACAP in the hypophysectomized rat testis. The results suggest that both testicular PACAP and its mRNA expression are regulated by the hypothalamic-pituitary-gonadal activity, and that FSH may play a major role in this regulation.
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PMID:Effect of hypophysectomy on pituitary adenylate cyclase-activating polypeptide gene expression in the rat testis. 853 85


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