Skip to main content
SpringerLink
Log in

Reserpine-induced depletion of neuropeptide Y from cardiovascular nerves and adrenal gland due to enhanced release

  • Rudolf Buchheim Lecture
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

  1. 1.

    The mechanisms underlying reserpine-induced depletion of neuropeptide Y-like immunoreactivity (NPY-LI) in relation to tissue content of noradrenaline (NA) and cardiovascular impairment were studied in guinea-pigs.

  2. 2.

    Reserpine pretreatment (5 mg/kg SC) caused a 5-fold increase in plasma levels of NPY-LI with a maximum after 4 h. This was associated with a progressive fall in systemic arterial blood pressure and heart rate (to about 50% of basal values). The contents of NPY-LI and NA in nerves of the heart and quadriceps muscle were then reduced by about 75% and 85%, respectively. The adrenal content of NPY-LI was reduced by 40% 8 h after reserpine, while the adrenaline content was uninfluenced.

  3. 3.

    Pretreatment with guanethidine depleted NA in the heart but did not influence plasma levels or tissue content of NPY-LI per se. The reserpine-induced increase in plasma NPY-LI and the depletion of NPY-LI in the heart and skeletal muscle was to a large extent prevented by guanethidine. The reserpine-induced bradycardia and hypotension were reduced after guanethidine pretreatment.

  4. 4.

    Chlorisondamine pretreatment depressed heart rate, blood pressure and plasma levels of NPY-LI. Furthermore, chlorisondamine inhibited the reserpine-induced increase in plasma NPY-LI and prevented the reduction in tissue content of NPY-LI in the heart, skeletal muscle and adrenal. The tissue depletion of NA induced by reserpine, however, was not influenced by chlorisondamine. The reserpine-induced hypotension was reduced by chlorisondamine, while the bradycardia was not influenced.

  5. 5.

    In conclusion, reserpine pretreatment induced a marked increase in plasma NPY-LI in guinea-pigs. The plasma raise in NPY-LI was reduced by guanethidine, which is likely to inhibit NPY release from sympathetic terminals, and blocked by chlorisondamine which blocks sympathetic transmission at the ganglionic level, suggesting that reserpine caused an enhanced release of NPY from certain sympathetic nerves and adrenal gland. Enhanced release of NPY in excess of resupply caused by neurogenic activation and/or loss of local presynaptic inhibitory control of release due to NA depletion may therefore explain the reduction in tissue content of NPY-LI. Whether NPY depletion contributes to the cardiovascular impairment seen after reserpine remains of be established.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Arnaiz JM, Garcia AG, Horga JF, Kirpeker SM (1978) Tissue and plasma catecholamines and dopamine-beta-hydroxylase activity of various animal species after neurogenic sympathetic stimulation. J Physiol 285:515–529

    Google Scholar 

  • Benmilaud M (1963) The bretylium-like effect of guanethidine. Life Sciences 1:9–15

    Google Scholar 

  • Boura A, Green AF (1965) Adrenergic neurone blocking agents. Ann Rev Pharm 5:183–212

    Google Scholar 

  • Carlsson A (1965) Drugs which block the storage of 5-hydroxytryptamine and related amines. In: Erspamer V (ed) Handbook Exp Pharm, vol 19. Springer, Berlin Heidelberg New York, pp 529–592

    Google Scholar 

  • Chang C, Costa E, Brodie BB (1965) Interaction of guanethidine with adrenergic neurons. J Pharm Exp Ther 147:303–312

    Google Scholar 

  • Cripps H, Dearnaley D (1972) Vascular response and noradrenaline overflows in the isolated blood-perfused cat spleen: some effects of cocaine, normetanephrine and alpha-blocking agents. J Physiol 227:647–664

    Google Scholar 

  • Cubeddu LX, Barnes E, Langer SZ, Weiner N (1974) Release of norepinephrine and dopamine-beta-hydroxylase by nerve stimulation. I. Role of neuronal and extraneuronal uptake and of alpha-presynaptic receptors. J Pharmacol Exp Ther 190: 431–450

    Google Scholar 

  • Cubeddu LX, Weiner N (1975) Release of norepinephrine and dopamine-beta-hydroxylase by nerve stimulation. V. Enhanced release associated with a granular effect of a benzoquinolizine derivative with reserpine-like properties. J Pharm Exp Ther 193:757–774

    Google Scholar 

  • Dahlström A, Häggendahl J (1966) Studies on the transport and life-span of amine storage granules in a peripheral adrenergic neuron system. Acta Physiol Scand 67:287–288

    Google Scholar 

  • Dontas AS (1957) Effects of reserpine and hydralazine on carotid and splanchnic nerve activity and blood pressure. J Pharm Exp Ther 121:1–7

    Google Scholar 

  • Fielden R, Coreen AC (1967) A comparative study of the noradrenaline-depleting and sympathetic blocking actions of guanethidine and beta-hydroxyphenethyl-guanethidine. Br J Pharmac Chemother 30:155–165

    Google Scholar 

  • Fried G, Lundberg JM, Theodorsson-Norheim E (1985a) Subcellular storage and axonal transport of neuropeptide Y (NPY) in relation to catecholamines in the cat. Acta Physiol Scand 125:145–154

    Google Scholar 

  • Fried G, Terenius L, Hökfelt T, Goldstein M (1985b) Evidence for differential localization of noradrenaline and neuropeptide Y (NPY) in neuronal storage vesicles isolated from rat vas deferens. J Neuroscience 5:450–458

    Google Scholar 

  • Hertting G, Axelrod J, Patrick RW (1962a) Actions of bretylium and guanethidine on the uptake and release of 3H-noradrenaline. Brit J Pharmacol 18:161–166

    Google Scholar 

  • Hertting G, Potter L, Axelrod J (1962b) Effects of decentralization and ganglionic blocking agents on the spontaneous release of 3H-norepinephrine. J Pharmacol 136:289–292

    Google Scholar 

  • Holzbauer M, Vogt M (1956) Depression by reserpine of the noradrenaline concentration in the hypothalamus of the cat. J Neurochemistry 1:8–11

    Google Scholar 

  • Iggo A, Vogt M (1960) Preganglionic sympathetic activity in normal and reserpine-treated cats. J Physiol (Lond) 150:114–133

    Google Scholar 

  • Lundberg JM, Tatemoto K (1982) Pancreatic polypeptide family APP, BPP, NPY and PYY) in relation to sympathetic vasoconstriction resistant to alpha-adrenoceptor blockade. Acta Physiol Scand 116:393–402

    Google Scholar 

  • Lundberg JM, Terenius L, Hökfelt T, Martling C-R, Tatemoto K, Mutt V, Polak J, Bloom SR (1982) Neuropeptide Y (NPY)-like immunoreactivity in peripheral noradrenergic neurons and effects of NPY on sympathetic function. Acta Physiol Scand 116:477–480

    Google Scholar 

  • Lundberg JM, Terenius L, Hökfelt T, Goldstein M (1983) High levels of neuropeptide Y in peripheral noradrenergic neurons in various mammals including man.Neurosc Letters 42:167–172

    Google Scholar 

  • Lundberg JM, Hua X, Franco-Cereceda A (1984a) Effects of neuropeptide Y (NPY) on mechanical activity and neurotransmission in the heart, vas deferens and urinary bladder of the guinea-pig. Acta Physiol Scand 121:325–332

    Google Scholar 

  • Lundberg JM, Änggård A, Theodorsson-Norheim E, Pernow J (1984b) Guanethidine-sensitive release of neuropeptide Y-like immunoreactivity in the cat spleen by sympathetic nerve stimulation. Neurosc Letters 52:175–180

    Google Scholar 

  • Lundberg JM, Saria A, Änggård A, Hökfelt T, Terenius L (1984c) Neuropeptide Y and noradrenaline interaction in peripheral cardiovascular control. Clin Exp Theory Pract A 6:1961–1972

    Google Scholar 

  • Lundberg JM, Fried G, Pernow J, Theodorsson-Norheim E (1985a) Co-release of neuropeptide Y and catecholamines upon adrenal activation in the cat. Acta Physiol Scand (in press)

  • Lundberg JM, Rudehill A, Sollevi A, Theodorsson-Norheim E, Hamberger B (1985b) Frequency and reserpine-dependent chemical coding of sympathetic transmission: Differential release of noradrenaline and neuropeptide Y from pig spleen. Neurosc Letters (in press)

  • Lundberg JM, Saria A, Franco-Cereceda A, Hökfelt T, Terenius L, Goldstein M (1985c) Differential effects of reserpine and 6-hydroxydopamine on neuropeptide Y (NPY) and noradrenaline in peripheral neurons. Naunyn-Schmiedeberg's Arch Pharmacol 328:331–340

    Google Scholar 

  • Lundberg JM, Saria A, Franco-Cereceda A, Theodorsson-Norheim E (1985d) Treatment with sympatholytic drugs changes content of neuropeptide Y in cardiovascular nerves and adrenal gland. Acta Physiol Scand 124:603–611

    Google Scholar 

  • Reid JL, Kopin IJ (1975) The effects of ganglionic blockade, reserpine and vinblastine on plasma catecholamines and dopamine-beta-hydroxylase in the rat. J Pharm Exp Ther 193:748–756

    Google Scholar 

  • Rosell S, Sedvall G (1962) The rate of disappearance of vasco-constrictor responses to sympathetic chain stimulation after reserpine treatment. Acta Physiol Scand 56:306–314

    Google Scholar 

  • Sedvall G (1964) Short-term effects of reserpine on noradrenaline levels in skeletal muscle. Acta Physiol Scand 62:101–108

    Google Scholar 

  • Theodorsson-Norheim E,Hemsén A, Lundberg JM (1985) Radioimmunoassay for NPY: Chromatographic characterization of immunoreactivity in plasma and tissue extracts. Scand J Clin Lab Invest 45:355–365

    Google Scholar 

  • Viveros OH, Arqueros L, Connett RJ, Kirsher N (1969) Mechanism of secretion from the adrenal medulla. IV. The fate of the storage vesicles following insulin and reserpine administration. Mol Parmacol 5:69–82

    Google Scholar 

  • Weiner N, Perkins M, Lysman RL (1962) Effect of reserpine on noradrenaline content of innervated and denervated brown adipose tissue of the rat. Nature 193:137–138

    Google Scholar 

  • Wu P, Penman E, Coy DH, Reest H (1983) Evidence for direct production of somatostatin-14 from a large precursor than somatostatin-28 in a phaeochromocytoma. Reg Peptides 5:219–224

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Karolinska Institutet, Box 60400, S-104 01, Stockholm, Sweden

    Jan M. Lundberg & Ahmad Al-Saffar

  2. Department of Experimental and Clinical Pharmacology, University of Graz, Universitätsplatz 4, A-8010, Graz, Austria

    Alois Saria

  3. Department of Clinical Chemistry, Karolinska Hospital, Box 60500, S-104 01, Stockholm, Sweden

    Elvar Theodorsson-Norheim

Authors
  1. Jan M. Lundberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ahmad Al-Saffar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alois Saria
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elvar Theodorsson-Norheim
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lundberg, J.M., Al-Saffar, A., Saria, A. et al. Reserpine-induced depletion of neuropeptide Y from cardiovascular nerves and adrenal gland due to enhanced release. Naunyn-Schmiedeberg's Arch. Pharmacol. 332, 163–168 (1986). https://doi.org/10.1007/BF00511407

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00511407

Key words

Search

Navigation