EFFECTS OF COLCHICINE AND VINBLASTINE ON AXONAL TRANSPORT AND TRANSMITTER RELEASE IN SYMPATHETIC NERVES

Microtubules were first observed in neurons fifteen years ago.' In neurons, as in other cell types, these tubular structures have an outer diameter of approximately 240 A, a wall thickness of approximately 50 A, and a low-density central core of 140 A in diameter. Microtubules appear to be rigid, unbranched structures that extend continuously from the cell body into the axons and dendrites. Some of the known functions of microtubules include endowment of long cellular processes with structural integrity, movement of chromosomes in mitosis, and dispersion and constriction of melanin granules along with melanocyte processes in response to a variety of stimuli. (See Ref. 2 for review of above.) The specific microtubular protein was first isolated by exploiting the ability of the alkaloid colchicine to bind this protein ~pecifically.~~ I When incubated with microtubules, the initial effect of colchicine is to disaggregate the structures into their constituent filaments.5 'I'ubulin, the subunit protein of microtubules, has been isolated and found to have a molecular weight of approximately 120,000.6~ The protein is highly acidic and contains large amounts of glycine and proline.61 The colchicine-binding protein of the microtubules was found to be identical with the protein subunit of 60,000 molecular Colchicine was found to interfere with a number of other cell functions, including mitosis,s movement of melanin granules,9 and saltatory movement.lo Another alkaloid, vinblastine, disaggregates tubules of mitotic spindles and spinal cord motor neurons.5 The possible role of microtubules in axonal transport was recently reviewed by Schmitt.? Additionally, based on work in a number of diverse cell and organ systems, it has been proposed that microtubules may play a role in the exocytotic mechanism for release of a variety of hormones.11-13 We wish to review our findings regarding the effects of colchicine and vinblastine on axonal transport and neurotransmitter release in peripheral noradrenergic neurons of several mammalian species.

[1]  O. J. Eigsti,et al.  Colchicine in Agriculture, Medicine, Biology and Chemistry , 2013 .

[2]  I. Meza,et al.  THE MECHANISM OF ACTION OF COLCHICINE , 1973, The Journal of cell biology.

[3]  J. Coyle,et al.  AXONAL TRANSPORT OF CATECHOLAMINE SYNTHESIZING AND METABOLIZING ENZYMES , 1973, Journal of neurochemistry.

[4]  G. Wooten,et al.  Enhanced release of dopamine -hydroxylase and norepinephrine from sympathetic nerves by dibutyryl cyclic adenosine 3', 5'-monophosphate and theophylline. , 1973, Molecular pharmacology.

[5]  W. Nicklas,et al.  Actomyosin-Like Protein in Brain Actomyosin-like protein may function in the release of transmitter material at synaptic endings , 1973 .

[6]  W. Douglas,et al.  Colchicine inhibits adrenal medullary secretion evoked by acetylcholine without affecting that evoked by potassium , 1972, British journal of pharmacology.

[7]  J. Trifaró,et al.  Inhibition by colchicine and by vinblastine of acetylcholine-induced catecholamine release from the adrenal gland: an anticholinergic action, not an effect upon microtubules. , 1972, Molecular pharmacology.

[8]  G. Wooten,et al.  Inhibition of release of dopamine- -hydroxylase and norepinephrine from sympathetic nerves by colchicine, vinblastine, or cytochalasin-B (hypogastric nerve stimulation-exocytosis-microtubules-microfilaments-guinea pig). , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[9]  R. Weinshilboum,et al.  Proportional Release of Norepinephrine and Dopamine-β-Hydroxylase from Sympathetic Nerves , 1971, Science.

[10]  A. Poisner,et al.  A possible role of microtubules in catecholamine release from the adrenal medulla: effect of colchicine, vinca alkaloids and deuterium oxide. , 1971, The Journal of pharmacology and experimental therapeutics.

[11]  N. K. Wessells,et al.  Microfilaments in Cellular and Developmental Processes , 1971, Science.

[12]  J. Wolff,et al.  Possible role of microtubules in thyroid secretion. , 1970, Proceedings of the National Academy of Sciences of the United States of America.

[13]  D. Mayor,et al.  An electron microscopic study of the early changes proximal to a constriction in sympathetic nerves , 1969, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[14]  S. Malawista,et al.  Histamine release from rat peritoneal mast cells: inhibition by colchicine and potentiation by deuterium oxide. , 1968, The Journal of pharmacology and experimental therapeutics.

[15]  P. Lacy,et al.  New Hypothesis of Insulin Secretion , 1968, Nature.

[16]  E. Taylor,et al.  PROPERTIES OF THE PROTEIN SUBUNIT OF CENTRAL-PAIR AND OUTER-DOUBLET MICROTUBULES OF SEA URCHIN FLAGELLA , 1968, The Journal of cell biology.

[17]  H. Wiśniewski,et al.  EFFECTS OF MITOTIC SPINDLE INHIBITORS ON NEUROTUBULES AND NEUROFILAMENTS IN ANTERIOR HORN CELLS , 1968, The Journal of cell biology.

[18]  P. Laduron,et al.  Evidence for an Extragranular Localization of Tyrosine Hydroxylase , 1968, Nature.

[19]  E. Taylor,et al.  ISOLATION OF A PROTEIN SUBUNIT FROM MICROTUBULES , 1967, The Journal of cell biology.

[20]  G. Borisy,et al.  THE MECHANISM OF ACTION OF COLCHICINE , 1967, The Journal of cell biology.

[21]  G. Borisy,et al.  THE MECHANISM OF ACTION OF COLCHICINE , 1967, The Journal of cell biology.

[22]  J. Axelrod,et al.  PROPERTIES OF NOREPINEPHRINE STORAGE PARTICLES OF THE RAT HEART. , 1963, The Journal of pharmacology and experimental therapeutics.

[23]  K. Roberts,et al.  Cytoplasmic microtubules and their functions. , 1974, Progress in biophysics and molecular biology.

[24]  W. Nicklas,et al.  Actomyosin-like protein in brain. , 1973, Science.

[25]  P. Banks,et al.  Intra-axonal transport in noradrenergic neurons in the sympathetic nervous system. , 1972, Biochemical Society symposium.

[26]  A. Dahlström.  Axoplasmic transport (with particular respect to adrenergic neurons). , 1971, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[27]  P. Laduron,et al.  Transport of noradrenaline and dopamine-β-hydroxylase in sympathetic nerves , 1968 .