Effects of vinblastine on neuropeptide Y levels in the sympathoadrenal system, bone marrow and thrombocytes of the rat.
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 microtubuli function and/or neuronal activation.
Hemsén
A
A
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Pernow
J
J
Millberg
B I
BI
Lundberg
J M
JM
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism*; D003714:Denervation; D004837:Epinephrine / Q000097:blood / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009478:Neuropeptide Y / Q000097:blood / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D014747:Vinblastine / Q000494:pharmacology*
D009478:Neuropeptide Y; D014747:Vinblastine; D009638:Norepinephrine; D004837:Epinephrine