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Effects of vinblastine on neuropeptide Y levels in the sympathoadrenal system, bone marrow and thrombocytes of the rat

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Abstract

The dose-related and time-related effects of vinblastine on tissue, platelet and plasma content of neuropeptide Y (NPY) were investigated in the rat and compared to the effects on catecholamine (CA) content. CA was quantified by HPLC with electrochemical detection and NPY-like immunoreactivity (LI) was analyzed by radioimmunoassay (RIA). Vinblastine (3.0 mg/kg, i.v.) decreased levels of both NPY-LI and CA after 48 h in the kidney, vas deferens and adrenal gland, whereas in the coeliac ganglion and bone marrow vinblastine induced an increase of NPY-LI which occurred already at a dose of 0.3 mg/kg. Also the content of NPY-LI in platelet-poor plasma and platelets as well as the decapitation-induced increase of plasma levels of noradrenaline (NA) and adrenaline (A) were attenuated by vinblastine (3.0 mg/kg). The elevation of NPY-LI content in the kidney, coeliac ganglion and bone marrow as well as the reduced levels of NPY-LI in platelets and platelet-poor plasma was observed already after 24 hours, whereas the reduction of NPY-LI and CA in the kidney and adrenal gland was present after 2 days. Vinblastine caused a biphasic effect on the content of NPY-LI in the sympathetic nerves of the kidney with an initial increase (by 120% at 24 h) followed by a decrease (by 79% at 4 days). The effect on NA-levels, however, was only a decrease. The axonal transport of NPY-LI as revealed by accumulation above a ligation of the sciatic nerve was reduced by 27% 2 days after vinblastine 3 mg/kg. The vinblastine-evoked depletion of NPY-LI and catecholamines in the kidney as well as in the adrenal was largely prevented by chlorisondamine, a nicotinic ganglionic blocking agent, suggesting that preganglionic neuronal activity was a key factor for this effect, in contrast to the influence on the coeliac ganglion cells and the megakaryocytes in the bone marrow. Furthermore, the delayed vinblastine depletion of NPY-LI in the kidney resembled the influence of surgical axotomy while reserpine caused a more rapid and complete depletion of both NPY-LI and NA. It is concluded that the multiple effects of vinblastine on sympathetic nerves, adrenal gland and megakaryocytes/thrombocytes can be monitored by analysis of NPY and be related to interference with microbutuli function and/or neuronal activation.

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Authors and Affiliations

  1. Department of Pharmacology, Karolinska Institutet, Box 60400, S-10401, Stockholm, Sweden

    A. Hemsén, J. Pernow, B. -I. Millberg & J. M. Lundberg

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  1. A. Hemsén
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  2. J. Pernow
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  3. B. -I. Millberg
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  4. J. M. Lundberg
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Hemsén, A., Pernow, J., Millberg, B.I. et al. Effects of vinblastine on neuropeptide Y levels in the sympathoadrenal system, bone marrow and thrombocytes of the rat. Agents and Actions 34, 429–438 (1991). https://doi.org/10.1007/BF01988740

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  • DOI: https://doi.org/10.1007/BF01988740

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