UNIPROT:P01275 - FACTA Search

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Query: UNIPROT:P01275 (glucagon)
26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preganglionic nerve stimulation leads to an acute elevation of tyrosine hydroxylase (TH) activity in the rat superior cervical ganglion. This effect is mediated in part by acetylcholine, acting via nicotinic receptors, and in part by a noncholinergic neurotransmitter. As a first step in an attempt to identify this noncholinergic transmitter, we have examined a number of biogenic amines, purine nucleotides, neuropeptides, and other compounds for their ability to increase TH activity. Secretin, vasoactive intestinal peptide (VIP), and PHI (a 27-amino acid peptide with an NH2-terminal histidine and a COOH-terminal isoleucine amide), all members of the secretin family of peptides, increased TH activity acutely. Human pancreatic growth hormone-releasing factor, glucagon, and gastric inhibitory peptide (three other members of this peptide family) and all other transmitter candidates tested had no effect on this enzyme activity. We have examined the possibility that this peptidergic regulation of TH activity is mediated via changes in adenosine 3',5'-cyclic monophosphate (cAMP) levels. When the six members of the secretin family were tested for their ability to increase cAMP levels in the ganglion, secretin, VIP, and PHI significantly increased this cyclic nucleotide, whereas growth hormone-releasing factor, glucagon, and gastric inhibitory peptide produced no significant effects. The rank orders of potency and of efficacy of secretin, VIP, and PHI in altering TH activity and cAMP levels were identical. Furthermore, a strong correlation was found between the cAMP level and the TH activity in individual ganglia exposed to these peptides. Finally, 8-bromoadenosine 3',5'-cyclic monophosphate and forskolin also increased TH activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of the concentration of adenosine 3',5'-cyclic monophosphate and the activity of tyrosine hydroxylase in the rat superior cervical ganglion by three neuropeptides of the secretin family. 286 28

We surveyed retinas of Raja erinacea, Mustelus canis, and Squalus acanthias for neurotransmitter substances by using antisera directed against the substances themselves or against their synthesizing enzymes. Both the peroxidase-antiperoxidase (PAP) and indirect fluorescent techniques were employed to visualize the primary antisera. In all three species positive results were obtained with antisera directed against tyrosine hydroxylase (TOH), glutamic acid decarboxylase (GAD), serotonin (5-HT), and leucine enkephalin (Lenk). Antisera directed against glucagon, neurotensin, beta-endorphin, vasoactive intestinal peptide, or bombesin failed to show any specific staining. Immunoreactivity was located in amacrine, interplexiform, and horizontal cells as well as in axons of the optic fiber layer. The four antisera labelled different amacrine cell classes, distinguished on the bases of perikaryal morphology and the distribution of cell processes in the inner plexiform layer (IPL). Amacrine cells that labelled with the same marker were seen to have different morphologies in the species studied. Thus, TOH-like immunoreactivity was distributed in layers 1, 3, and 5 of the IPL in Mustelus but only in layers 1 and 3 in Raja retina. GAD-like immunoreactivity was found diffusely over all layers of the IPL in Raja, but in Mustelus it was confined primarily to layers 1, 3, and 5 of the IPL. Lenk- and 5-HT-like immunoreactivities showed similar species variations. Two neurochemical classes of interplexiform cell were identified in this study. In Mustelus GAD-like and Lenk-like immunoreactive interplexiform cells were seen whereas in Raja only GAD-positive interplexiform cells were detected. In squalus no unequivocal demonstration of any interplexiform cell was made with these antisera. The GAD antiserum also labelled a subset of the horizontal cells in the dorsal retina of Raja. TOH and 5-HT-antisera labelled axons in the optic fiber layer of all three species but reactive ganglion cell perikarya were not identified.
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PMID:Retinal neurochemistry of three elasmobranch species: an immunohistochemical approach. 286 65

The pancreatic islets of mouse embryos are comprised of four different endocrine cell types and of cells containing a hormone (i.e., glucagon) and a catecholamine enzyme (tyrosine hydroxylase, TH) which appear sequentially during development in vivo. The presence of TH in glucagon cells, however, is transient, since adult pancreatic A cells do not express the enzyme. In this study we sought to determine whether the endocrine precursor cells are primed to differentiate and express catecholamine enzymes during their maturation following a predetermined sequence or whether these processes are regulated by environmental cues. To answer this question, we used immunocytochemical procedures to examine the differentiation of pancreatic rudiments removed from E11 mouse embryos and maintained in culture and of pancreases that regenerated in vitro from E11 pancreatic ducts. We found that although all the endocrine cell types differentiate in the gland in culture, the sequence of their appearance is different from that in vivo, suggesting that the timing of differentiation may be regulated by environmental factors. We also found that, in vitro, the pancreas contains TH-glucagon cells, indicating that the expression of the enzyme by pancreatic A cells is independent of factors present in vivo. Moreover, the fact that the TH-glucagon cells also differentiate during pancreatic regeneration suggests that the expression of the enzyme may be a characteristic stage of endocrine cell precursors during maturation.
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PMID:Differentiation of prospective mouse pancreatic islet cells during development in vitro and during regeneration. 288 18

We have previously reported that cells transiently expressing tyrosine hydroxylase (TH), the first enzyme of the catecholamine biosynthetic pathway, are present in the pancreas of mouse embryos from prenatal Day 11 (E11) and that, at E12, some TH cells contain glucagon. Cells containing TH were also found in adults which, unlike the TH cells of embryos, did not contain glucagon (G. Teitelman, T. H. Joh, and D. J. Reis (1981). Proc. Natl. Acad. Sci. 78, 5225). These findings suggested to us that the TH cells of embryonic pancreas were the precursors of glucagon cells of adults. In this study we used immunocytochemical and autoradiographic techniques to determine whether cells containing TH (a) were present in pancreas throughout pre- and postnatal development, (b) were localized to a specific region of the gland, (c) contained insulin at any time, and (d) proliferated. We found that TH cells were present in pancreas throughout life. In embryos, cells containing TH localized only along the pancreatic duct, also contained either glucagon or insulin, and were able to proliferate. In contrast, after birth, the pancreatic duct contained no TH cells. Cells containing TH in postnatal and adult mice also differed from embryonic TH cells in that they were found in all islets, contained insulin but not glucagon, and did not synthesize DNA, and hence did not proliferate. These findings suggest that progenitor cells that contain catecholamines and are present in the pancreatic duct give rise to glucagon and insulin cells of adult islets. They also indicate that the TH-insulin cells of postnatal and adult mice are not stem cells but are postmitotic cells that appear in the islets after birth.
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PMID:Cell lineage analysis of pancreatic islet development: glucagon and insulin cells arise from catecholaminergic precursors present in the pancreatic duct. 288 53

Insulin appears in the developing mouse pancreas at embryonic day 12 (e12). Transgenic mice harboring three distinct hybrid genes utilizing insulin gene regulatory information first express the transgene product two days earlier, at e10, in a few cells of the pancreatic bud. Throughout development and postnatal life, all of the insulin-producing (beta) cells coexpress the hybrid insulin gene. In addition, islet cells containing glucagon, somatostatin, pancreatic polypeptide, and the neuronal enzyme tyrosine hydroxylase coexpress the transgene when they first arise. Similarly, coexpression of these normally distinct islet cell markers occurs during differentiation of the four endocrine cell types. The transgene product also appears transiently during embryogenesis in cells of the neural tube and in neural crest. The results suggest a common precursor for the endocrine cells of the pancreas. Moreover, they imply a relationship between neural and pancreatic endocrine tissue.
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PMID:Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons. 328 75

In embryonic mice, the catecholamine biosynthetic enzyme tyrosine hydroxylase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] can be visualized immunocytochemically in a population of cells in epithelial cords of the developing pancreas. These embryonic catecholamine cells, first seen by day 11, are large and vacuolated and have a folded nuclear membrane. One day later, at day 12, glucagon is first detected immunocytochemically in pancreatic cells similar in location and morphology to the embryonic catecholamine cells. By use of a method for detecting both antigens in the same cell, both the hydroxylase and glucagon can be visualized between day 12 and day 14 in 10-40% of stained cells. From day 14, the number of cells stained for hydroxylase decreases; they cannot be detected after day 18. In contrast, the cells containing glucagon increase during development and persist throughout life. Endocrine cells of the embryonic pancreas also contain dopa decarboxylase but not dopamine-beta-hydroxylase or phenylethanolamine-N-methyl transferase. In adult mice, small cells containing tyrosine hydroxylase but differing in location and morphology from the embryonic catecholaminergic cells are seen in pancreatic islets. The adult catecholaminergic cells never store glucagon. We suggest that adult glucagon (A)-containing cells arise from transformation in situ of cells that transiently express a catecholaminergic (probably dopaminergic) phenotype. These results suggest that one class of peptidergic cells may arise from transformation of an aminergic precursor.
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PMID:Transformation of catecholaminergic precursors into glucagon (A) cells in mouse embryonic pancreas. 611 53

A population of cells containing the enzymes tyrosine hydroxylase (TH) and dopa-decarboxylase (L-AADC) but not dopamine-B-hydroxylase (DBH) nor phenylethanolamine-N-methyltransferase (PNMT) can be detected with immunocytochemical techniques in the pancreas of mouse embryos at the 11th day of development (E 11). The presence of TH in embryonal pancreas is transient: TH is not observed after E 15. By use of a method for simultaneously detecting two antigens in the same section both TH and glucagon were visualized in the same cell on E 12. Double labelled cells comprised 10% of all stained cells. At E 14.5, some of the cells stained for TH also contained insulin. However, at the time somatostatin appeared no embryonal cells containing TH remained. We conclude that two cell types of the APUD series, i.e., the glucagon and insulin cells of pancreas, arise from transformation, in situ, of cells that transiently express a dopaminergic phenotype. These results suggest that peptide-containing cells in skin, brain and gut are linked by a common embryonic origin. They also raise the prospect that other peptidergic cells of the APUD series may have aminergic precursors.
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PMID:Linkage of the brain-skin-gut axis: islet cells originate from dopaminergic precursors. 612 86

We have previously shown that stimulation of the preganglionic cervical sympathetic trunk leads to an acute increase in tyrosine hydroxylase (TyrOHase) activity in the rat superior cervical ganglion. This increase appears to be mediated in part by acetylcholine and in part by a second neurotransmitter. As a first step in an attempt to determine the identity of this noncholinergic transmitter, we have examined the ability of a number of neuropeptides to increase ganglionic TyrOHase activity in vitro. Secretin and vasoactive intestinal peptide (VIP) both stimulated TyrOHase activity, whereas angiotensin II, bombesin, bradykinin, cholecystokinin octapeptide, glucagon, insulin, luteinizing hormone-releasing hormone, [D-Ala(2), Met(5)]enkephalinamide, motilin, neurotensin, somatostatin, and substance P produced no effects. Secretin produced a significant increase in TyrOHase activity at 1 nM and a maximal elevation at 0.1 muM. VIP produced a significant increase at 0.1 muM and a near maximal effect at 10 muM. Although secretin was about 2 orders of magnitude more potent than VIP, it produced a significantly smaller maximal increase in enzyme activity. Incubation of ganglia with both secretin (10 muM) and VIP (10 muM) produced an increase in TyrOHase activity that was not significantly different from that produced by VIP alone. The stimulatory effects of secretin and VIP were reversible within minutes after removal of the peptides. Neither incubation of intact ganglia with the cholinergic antagonists hexamethonium and atropine nor prior decentralization of ganglia altered the response to the peptides. Thus, the data demonstrate that secretin and VIP acutely increase TyrOHase activity in the superior cervical ganglion and suggest that they produce this effect by acting directly on ganglionic neurons. It remains to be determined whether secretin or VIP or a related peptide is released during preganglionic nerve firing and whether one or more of these peptides is responsible for the noncholinergic elevation of TyrOHase activity produced by preganglionic nerve stimulation.
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PMID:Secretin and vasoactive intestinal peptide acutely increase tyrosine 3-monooxygenase in the rat superior cervical ganglion. 613 May 26

We have examined the ability of a number of neuropeptides to increase tyrosine hydroxylase (TH) activity in the superior cervical ganglion in vitro. Secretin and vasoactive intestinal peptide (VIP) both increased TH activity, whereas angiotensin II, bombesin, bradykinin, cholecystokinin octapeptide, insulin, luteinizing hormone-releasing hormone, [D-Ala2, Met5]enkephalinamide, motilin, neurotensin, somatostatin, and substance P produced no effects. Secretin and VIP increased TH activity with an EC50 of 5 nM and 0.5 microM, respectively. The effects of these peptides were not altered by prior decentralization of the ganglia, by addition of hexamethonium (3 mM) and atropine (6 microM), or by lowering the concentration of calcium in the medium to 0.1 mM. Addition of carbachol (3 microM) potentiated the effects of both secretin and VIP on TH activity. Several gastrointestinal peptides with structural similarities to secretin and VIP were examined for their ability to increase TH activity. Glucagon, gastric inhibitory peptide and human pancreatic tumor growth hormone-releasing factor produced no effect at a concentration of 10 microM, while PHI increased enzyme activity.
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PMID:Acute stimulation of ganglionic tyrosine hydroxylase activity by secretin, VIP and PHI. 614 16

An immunohistochemical and immunoelectron microscopic study was used to demonstrate tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) immunoreactivities in the rat pancreas. Small TH immunoreactive cells were found in close contact with large TH immunonegative ganglion cells among the exocrine glands and were occasionally found in some islets. Some of these TH immunoreactive cells were also DBH immunopositive. The immunoreaction product was seen diffusely in the cytoplasm and in the granule cores of TH immunoreactive cells. All intra-pancreatic ganglion cells were immunoreactive for DBH, but not for TH. The TH immunoreactive cells were identified as small intensely fluorescent (SIF) cells due to their localization and morphological characteristics and showed no insulin, glucagon, somatostatin or pancreatic polypeptide immunoreactivities. These results indicate that SIF cells may release dopamine or noradrenaline to adequate stimuli while the intra-pancreatic ganglion cells with only DBH may not synthesize catecholamines in a normal biosynthetic pathway. TH immunoreactive nerve bundles without varicosities and fibers with varicosities, associated or unassociated with blood vessels, were found in both the exocrine and endocrine pancreas. Close apposition of TH immunoreactive nerve fibers to the smooth muscle and endothelial cells of the blood vessels was observed. A close apposition between TH immunoreactive nerve fibers and exocrine acinar cells and islet endocrine cells was sometimes found in the pancreas. The immunoreaction product was seen diffusely in the axoplasm and in the granular vesicles of the immunoreactive nerve fibers. Since no TH immunoreactive ganglion cells were present in the rat pancreas, the present study suggests that noradrenergic nerve fibers in the pancreas may be extrinsic in origin, and may exert an effect on the regulation of blood flow and on the secretory activity of the acinar cells, duct cells and endocrine cells.
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PMID:Immunocytochemical study of tyrosine hydroxylase and dopamine beta-hydroxylase immunoreactivities in the rat pancreas. 752 36

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