Large Dense‐Core Vesicles in Rat Adrenal After Reserpine: Levels of mRNAs of Soluble and Membrane‐Bound: Constituents in Chromaffin and Ganglion Cells Indicate a Biosynthesis of Vesicles with Higher Secretory Quanta

Abstract: Rats were injected with a large dose of reserpine known to stimulate the adrenal medulla. Various times after drug treatment the mRNA levels of several constituents of large dense‐core vesicles were determined by northern blot analysis and in situ hybridization. The latter method allowed detection of changes in mRNA levels not only in chromaffin cells, but also in the ganglion cells found in adrenal medulla. Levels of the mRNAs of secretory components of large dense‐core vesicles (chromogranins A and B., secretogranin II, VGF, and neuropeptide Y) increased in chromaffin cells by 215–857% after 1–3 days of drug treatment. For partly membrane‐bound components (dopamine β‐hydroxylase, prohormone convertase 2, carboxypeptidase H., and peptidylglycine α‐amidating monooxygenase) the changes ranged from 182 to 315%, whereas for glycoprotein III and for intrinsic membrane proteins (cytochrome b661 and vesicle monoamine transporter 2) no change occurred. In ganglion cells the mRNAs that could be detected for VGF, neuropeptide Y., secretogranin II, carboxypeptidase H., and vesicle monoamine transporter 1 showed an analogous pattern of change, with significant increases for the secretory proteins and no change for the membrane components. From these and previous results we suggest the following concept: Long‐lasting stimulation of chromaffin cells or neurons does not induce the biosynthesis of a larger number of vesicles but rather leads to the formation of vesicles containing higher secretory quanta of chromogranins and neuropeptides. Key Words: ChromograninSecretogranin II—Monoamine transporter—Prohormone convertase 2—Carboxypeptidase H—Cytochrome b661‐Clusterin.

[1]  A. Laslop,et al.  Glycoprotein III (Clusterin, Sulfated Glycoprotein 2) in Endocrine, Nervous, and Other Tissues: Immunochemical Characterization, Subcellular Localization, and Regulation of Biosynthesis , 1993, Journal of neurochemistry.

[2]  S. Mahata,et al.  Reserpine causes differential changes in the mRNA levels of chromogranin B, secretogranin II, carboxypeptidase H, alpha-amidating monooxygenase, the vesicular amine transporter and of synaptin/synaptophysin in rat brain. , 1993, Brain research. Molecular brain research.

[3]  L. Devi,et al.  Dopamine antagonist haloperidol increases carboxypeptidase E mRNA in rat neurointermediate pituitary but not in various other rat tissues. , 1993, Brain research. Molecular brain research.

[4]  S. Mahata,et al.  Vesicle monoamine transporters 1 and 2: differential distribution and regulation of their mRNAs in chromaffin and ganglion cells of rat adrenal medulla , 1993, Neuroscience Letters.

[5]  S. Mahata,et al.  Concomitant Changes of Messenger Ribonucleic Acid Levels of Secretogranin II, VGF, Vasopressin and Oxytocin in thé Paraventricular Nucleus of Rats After Adrenalectomy and During Lactation , 1993, Journal of neuroendocrinology.

[6]  I. Fritz,et al.  Clusterin Insights into a multifunctional protein , 1993, Trends in Endocrinology & Metabolism.

[7]  R. Kirchmair,et al.  Histamine induces a gene-specific synthesis regulation of secretogranin II but not of chromogranin A and B in chromaffin cells in a calcium-dependent manner. , 1993, The Journal of biological chemistry.

[8]  L. Fricker,et al.  Regulation of Carboxypeptidase E by Membrane Depolarization in PC12 Pheochromocytoma Cells: Comparison with mRNAs Encoding Other Peptide‐ and Catecholamine‐Biosynthetic Enzymes , 1992, Journal of neurochemistry.

[9]  B. Hoffman,et al.  Expression cloning of a reserpine-sensitive vesicular monoamine transporter. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[10]  G. Sperk,et al.  Temporal lobe epilepsy of the rat: differential expression of mRNAs of chromogranin B, secretogranin II, synaptin/synaptophysin and p65 in subfields of the hippocampus , 1992 .

[11]  D. Eisenberg,et al.  A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter , 1992, Cell.

[12]  R. Fischer‐Colbrie,et al.  The chromogranins A and B: The first 25 years and future perspectives , 1992, Neuroscience.

[13]  A. Laslop,et al.  Effects of nerve growth factor on the biosynthesis of chromogranin A and B, secretogranin II and carboxypeptidase H in rat PC12 cells , 1992, Neuroscience.

[14]  S. Mahata,et al.  In situ hybridization: mRNA levels of secretogranin II, neuropeptides and carboxypeptidase h in brains of salt-loaded and brattleboro rats , 1992, Neuroscience.

[15]  D. Smith,et al.  Pituitary-specific transcriptional initiation sites of the rat carboxypeptidase-H gene and the influence of thyroid hormone status. , 1992, Molecular endocrinology.

[16]  N. Seidah,et al.  Distribution and regulation of the prohormone convertases PC1 and PC2 in the rat pituitary. , 1992, Molecular endocrinology.

[17]  I. Robinson,et al.  Reserpine‐Induced Processing of Chromogranin A in Cultured Bovine Adrenal Chromaffin Cells , 1992, Journal of neurochemistry.

[18]  A. Laslop,et al.  Immunological characterization of the endoproteases PC1 and PC2 in adrenal chromaffin granules and in the pituitary gland , 1992, FEBS letters.

[19]  A. Laslop,et al.  Sex‐Related Differences in Chromogranin A, Chromogranin B and Secretogranin II Gene Expression in Rat Pituitary , 1992, Journal of neuroendocrinology.

[20]  T. Hökfelt,et al.  Neuropeptide Y and catecholamine synthesizing enzymes and their mRNAs in rat sympathetic neurons and adrenal glands: Studies on expression, synthesis and axonal transport after pharmacological and experimental manipulations using hybridization techniques and radioimmunoassay , 1991, Neuroscience.

[21]  J. Kiss,et al.  Hypophysiotrophic neurons are capable of altering the ratio of co-packaged neurohormones , 1991, Neuroscience.

[22]  Y. S. Zhu,et al.  Transsynaptic activity regulates proenkephalin and tyrosine hydroxylase gene expression and the response to reserpine in the hamster adrenal. , 1991, Molecular pharmacology.

[23]  G. Sperk,et al.  Distribution of mRNAs for Chromogranins A and B and Secretogranin II in Rat Brain , 1991, The European journal of neuroscience.

[24]  D. Christie,et al.  Identification of kex2-related proteases in chromaffin granules by partial amino acid sequence analysis. , 1991, The Journal of biological chemistry.

[25]  K. Dong,et al.  Structure of the gene encoding VGF, a nervous system-specific mRNA that is rapidly and selectively induced by nerve growth factor in PC12 cells , 1991, Molecular and cellular biology.

[26]  A. Laslop,et al.  Stimulation of rat adrenal medulla can induce differential changes in the peptide and mRNA levels of chromogranins, neuropeptides and other constituents of chromaffin granules , 1991, Regulatory Peptides.

[27]  R. Fischer‐Colbrie,et al.  Common membrane proteins of chromaffin granules, endocrine and synaptic vesicles: Properties, tissue distribution, membrane topography and regulation of synthesis , 1990, Neurochemistry International.

[28]  A. Iwasa,et al.  Long lasting increase in neuropeptide Y gene expression in rat adrenal gland with reserpine treatment: positive regulation of transsynaptic activation and membrane depolarization. , 1990, Molecular pharmacology.

[29]  L. Ouafik,et al.  Thyroid Hormone Regulation of Peptidylglycine α-Amidating Monooxygenase Expression in Anterior Pituitary Gland , 1990 .

[30]  T. Hökfelt,et al.  Most ganglion cells in the rat adrenal medulla are noradrenergic. , 1990, Neuroreport.

[31]  R. Rigual,et al.  Reflex Splanchnic Nerve Stimulation Increases Levels of Carboxypeptidase E mRNA and Enzymatic Activity in the Rat Adrenal Medulla , 1990, Journal of neurochemistry.

[32]  Barbara J. Reaves,et al.  Comparison of the regulation of carboxypeptidase E and prolactin in GH4C1 cells, a rat pituitary cell line. , 1990, Neuroendocrinology.

[33]  M Chrétien,et al.  cDNA sequence of two distinct pituitary proteins homologous to Kex2 and furin gene products: tissue-specific mRNAs encoding candidates for pro-hormone processing proteinases. , 1990, DNA and cell biology.

[34]  A. Mcmahon,et al.  Rat dopamine β‐hydroxylase: Molecular cloning and characterization of the cDNA and regulation of the mRNA by reserpine , 1990 .

[35]  D. Steiner,et al.  Identification of a human insulinoma cDNA encoding a novel mammalian protein structurally related to the yeast dibasic processing protease Kex2. , 1990, The Journal of biological chemistry.

[36]  B. Eipper,et al.  Effect of secretagogues on components of the secretory system in AtT-20 cells. , 1990, Endocrinology.

[37]  A. Laslop,et al.  Insulin hypoglycemia increases the levels of neuropeptide Y and calcitonin gene-related peptide, but not of chromogranins A and B, in rat chromaffin granules , 1989, Regulatory Peptides.

[38]  B. Paterson,et al.  A protein induced by NGF in PC12 cells is stored in secretory vesicles and released through the regulated pathway. , 1989, The EMBO journal.

[39]  J. Dixon,et al.  Rat preprocarboxypeptidase H. Cloning, characterization, and sequence of the cDNA and regulation of the mRNA by corticotropin-releasing factor. , 1989, The Journal of biological chemistry.

[40]  D. Stoffers,et al.  Alternative mRNA splicing generates multiple forms of peptidyl-glycine alpha-amidating monooxygenase in rat atrium. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[41]  W. Young.  In situ hybridization histochemical detection of neuropeptide mRNA using DNA and RNA probes. , 1989, Methods in enzymology.

[42]  W. Huttner,et al.  The primary structure of rat secretogranin II deduced from a cDNA sequence. , 1988, Nucleic acids research.

[43]  L. Eiden,et al.  Neural and humoral factors separately regulate neuropeptide Y, enkephalin, and chromogranin A and B mRNA levels in rat adrenal medulla. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[44]  D. Larhammar,et al.  Neuropeptide tyrosine in the rat adrenal gland—immunohistochemical and in situ hybridization studies , 1988, Neuroscience.

[45]  H. Okayama,et al.  Primary structure of rat chromogranin A and distribution of its mRNA , 1988, FEBS letters.

[46]  P. Schofield,et al.  Structure of the precursor to an enzyme mediating COOH-terminal amidation in peptide biosynthesis. , 1987, Molecular endocrinology.

[47]  D. Scherman,et al.  Rat adrenal medulla: Levels of chromogranins, enkephalins, dopamine β-hydroxylase and of the amine transporter are changed by nervous activity and hypophysectomy , 1987, Neuroscience.

[48]  M. Griswold,et al.  Biosynthesis and molecular cloning of sulfated glycoprotein 2 secreted by rat Sertoli cells. , 1987, Biochemistry.

[49]  A. Laslop,et al.  Identification of two glycoproteins of chromaffin granules as the carboxypeptidase H , 1986, Neuroscience Letters.

[50]  T. Kanamatsu,et al.  Reflex splanchnic nerve stimulation increases levels of proenkephalin A mRNA and proenkephalin A-related peptides in the rat adrenal medulla. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[51]  R. Fischer‐Colbrie,et al.  Chromogranin C: A Third Component of the Acidic Proteins in Chromaffin Granules , 1986, Journal of neurochemistry.

[52]  N. Seidah,et al.  Immunocytochemical localization of a novel pituitary protein (7B2) within the rat brain and hypophysis. , 1985, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[53]  P. De Camilli,et al.  Secretogranins I and II: two tyrosine-sulfated secretory proteins common to a variety of cells secreting peptides by the regulated pathway , 1985, The Journal of cell biology.

[54]  O. H. Viveros,et al.  Regulation of opioid peptide synthesis and processing in adrenal chromaffin cells by catecholamines and cyclic adenosine 3':5'- monophosphate , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[55]  J. Dixon,et al.  Cloning, characterization, and DNA sequence of a human cDNA encoding neuropeptide tyrosine. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[56]  P. Giraud,et al.  Alternative modes of enkephalin biosynthesis regulation by reserpine and cyclic AMP in cultured chromaffin cells. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[57]  A. Weber,et al.  Isolation and Immunological Characterization of a Glycoprotein from Adrenal Chromaffin Granules , 1984, Journal of neurochemistry.

[58]  L. Kedes,et al.  Evolutionary conservation in the untranslated regions of actin mRNAs: DNA sequence of a human beta-actin cDNA. , 1984, Nucleic acids research.

[59]  S. Snyder,et al.  Enkephalin convertase: purification and characterization of a specific enkephalin-synthesizing carboxypeptidase localized to adrenal chromaffin granules. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[60]  D. Njus,et al.  Proton-Linked Transport in Chromaffin Granules1 , 1981 .

[61]  H. Winkler.  The biogenesis of adrenal chromaffin granules , 1977, Neuroscience.

[62]  M. Schwab,et al.  Increased specific activity of membrane‐bound dopamine β‐hydroxylase in chromaffin granules after reserpine treatment , 1977, Journal of neurochemistry.

[63]  H. Winkler.  The composition of adrenal chromaffin granules: An assessment of controversial results , 1976, Neuroscience.

[64]  H. Thoenen.  Comparison between the effect of neuronal activity and nerve growth factor on the enzymes involved in the synthesis of norepinephrine. , 1972, Pharmacological reviews.

[65]  A. D. Smith,et al.  Secretion of a Chromaffin Granule Protein, Chromogranin, from the Adrenal Gland after Splanchnic Stimulation , 1967, Nature.