Differential effects of reserpine and 6-hydroxydopamine on neuropeptide Y (NPY) and noradrenaline in peripheral neurons

Abstract

1. The effects of 6-hydroxydopamine (6-OHDA) and reserpine pretreatment on peripheral neuropeptide Y (NPY)-and noradrenaline (NA)-containing neurons were studied in guinea-pigs. 2. Ten days after 6-OHDA pretreatment, a 60–80% reduction of the NA content was observed in the right atrium of the heart, stellate ganglion and spleen. The content of NPY-like immunoreactivity (LI) was reduced by about 50% in the heart, not changed in the spleen while it increased to 200% of control in the stellate ganglion. Immunohistochemistry showed a pronounced loss of NPY-and tyrosinehydroxylase (TH)-immunoreactive (IR) nerves in the heart but not in the spleen. Increased NPY-IR was seen in axons and cell bodies of the stellate ganglion. 3. Reserpine pretreatment (thereshold dose 0.5 mg x kg⁻¹) caused a dose-and time-dependent reduction of the content of NPY-LI in the heart. A maximal depletion of NPY-LI (about 80%) was observed 5 days after reserpine. Reserpine pretreatment also reduced the content of NPY-LI in the spleen, while no significant change was observed in the adrenal gland or vas deferens. The levels of NPY-LI increased in the stellate ganglion to about 180% of control 5 days after reserpine. Immunohistochemical analysis revealed an almost total loss of NPY-IR nerve fibres in the heart as well as around blood vessels in the lung and skeletal muscle. No detectable changes were observed in perivascular NPY-IR nerves in the spleen, vas deferens or kidney. TH-IR nerves remained unchanged after reserpine, thus indicating that the observed loss of NPY-IR nerves was due to a depletion of NPY and not a degeneration. 4. No change in the levels of substance P-LI was observed in the right atrium 5 days after reserpine. 5. NA was, in contrast to NPY, markedly depleted in all tissues investigated after reserpine treatment. The depletion of NA was more extensive, and occurred more rapidly and at much lower doses as compared to the effects on NPY-LI. 6. Ligations of the sciatic nerve revealed that NPY-LI 4 was transported axonally with a rapid rate (3 mm/h). Reserpine pretreatment significantly increased the amount of accumulated NPY-IR above the ligation, suggesting an increase in axonal transport. 7. High performance liquid chromatography revealed that the NPY-LI consisted of two major peaks in the stellate ganglia, while only one peak closely corresponding to porcine NPY was seen in the right atrium. 8. In conclusion, 6-OHDA pretreatment depletes NPY-LI in certain terminal regions and increases NPY-LI in ganglia. Reserpine induces a tissue-and dose-dependent depletion of NPY-LI in certain terminal areas, while corresponding cell body content and axonal transport of the peptide seem to increase.