Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 343, Issue 4, pp 337–343 | Cite as

Differential effects of electrical stimulation, blockade of neuronal amine uptake and activation of α2-adrenoceptors on the release of endogenous noradrenaline and 5-hydroxytryptamine from the isolated rat pineal gland

  • K. Racké
  • M. Sommer
  • F. Burns
  • B. Hering


Isolated rat pineal glands were incubated in vitro and the release of endogenous noradrenaline or 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) was determined by HPLC with electrochemical detection. In the absence of test drugs, the spontaneous outflow of noradrenaline was about 10 fmol/10 min and electrical stimulation (5 Hz, 1500 pulses) evoked the release of about 70 fmol noradrenaline. Nomifensine enhanced the spontaneous outflow of noradrenaline about threefold and the electrically evoked release of noradrenaline about sixfold. In the presence of nomifensine, the α2-adrenoceptor antagonist yohimbine markedly increased the electrically evoked release of noradrenaline, whereas the α1-adrenoceptor antagonist prazosin had no effect. Clonidine inhibited the electrically evoked release of noradrenaline by about 65%, and this was antagonized by yohimbine in a competitive manner. In the absence of drugs, the initial spontaneous outflow of 5-HT was (compared with noradrenaline) very high 64 μmol/10 min. It declined by 80% within 1 h of incubation in vitro. The outflow of 5-HIAA amounted initially to 38 μmol/10 min and declined by 40% within 1 h of incubation. Addition of l-tryptophan (10 μmol/1) after 1 h of incubation in vitro largely enhanced the outflow of 5-HT and 5-HIAA within 30 min of incubation (about ten- and fourfold, respectively). When l-tryptophan was present from the onset of incubation the initial outflow of 5-HT and 5-HIAA was only slightly elevated, but the decline was largely attenuated. Neither omission of calcium nor addition of nomifensine, clonidine or yohimbine significantly affected the spontaneous outflow of 5-HT or 5-HIAA. Likewise, neither electrical stimulation in the absence or presence of nomifensine and yohimbine nor stimulation by high potassium (45 mmol/1) significantly affected the outflow of 5-HT or 5-HIAA.

In conclusion, the release of endogenous noradrenaline from the sympathetic nerves terminating in the pin eal gland is inhibited by presynaptic α2-adrenoceptors. The outflow of 5-HT from the pineal gland originates almost exclusively from non-neuronal cells, most probably the pinealocytes, and depends largely on a continuous de novo synthesis. Catabolism of 5-HT to 5-HIAA in the pineal gland occurs mainly in an extraneuronal compartment, probably the pinealocytes and/or the interstitial cells of the pineal gland.

Key words

Noradrenaline Serotonin Pineal gland α-Adrenoceptor l-Tryptophan 5-Hydroxyindoleacetic acid 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Axelrod J (1974) The pineal gland: a neurochemical transducer. Science 184:1341–1348CrossRefGoogle Scholar
  2. Azuma J, Vogel S, Josephson I, Sperelakis N (1977) Yohimbine blockade of ionic channels in myocardial cells. Eur J Pharmacol 51:109–119CrossRefGoogle Scholar
  3. Briggs GM, Meyer CF (1986) Effect of yohimbine on action potentials recorded from isolated canine ventricular myocytes. Eur J Pharmacol 127:125–128CrossRefGoogle Scholar
  4. Fuder H, Muscholl E, Spemann R (1983) The determination of presynaptic pA2 values of yohimbine and phentolamine on the perfused rat heart under conditions of negligible autoinhibition. Br J Pharmacol 79:109–119CrossRefGoogle Scholar
  5. Furchgott RE (1972) The classification of adrenoceptors (adrenergic receptors). An evaluation from the standpoint of receptor theory. In: Blaschko H, Muscholl E (eds) Handbook of Experimental Pharmacology, vol 33. Springer, Berlin Heidelberg New York, pp 283–335Google Scholar
  6. Jaim-Etcheverry G, Zieher LM (1971) Ultrastructural cytochemistry and pharmacology of 5-HT in adrenergic nerve endings: III. Selective increase of norepinephrine in the rat pineal gland consecutive to depletion of neuronal 5-hydroxytryptamine. J Pharmacol Exp Ther 178:42–48PubMedGoogle Scholar
  7. Jaim-Etcheverry G, Zieher LM (1983) Ultra-structural evidence for monoamine uptake vesicles of pineal sympathetic nerves immediately after their stimulation. Cell Tissue Res 233:463–469CrossRefGoogle Scholar
  8. Juillard MT, Collin JP (1979) Membranous sites of oxidative deamination: a comparison between ultracytochemical and radioautographic studies in the pineal organ of the wall lizard and the parakeet. Biol Cell 36:29–35Google Scholar
  9. Juillard MT, Collin JP (1980) Pools of serotonin in the pineal gland of the mouse: The mammalian pinealocyte as a component of diffuse neuroendocrine system. Cell Tissue Res 213:273–291CrossRefGoogle Scholar
  10. Koe BK (1976) Molecular geometry of inhibitors of the uptake of catecholamines and serotonin in synaptosomal preparations of rat brain. J Pharmacol Exp Ther 199:649–661PubMedGoogle Scholar
  11. Lu KS, Lin HS (1979) Cytochemical studies on cytoplasmic granular elements in the hamster pineal gland. Histochemistry 61:177–187CrossRefGoogle Scholar
  12. Müller J, Da Lage C (1977) Ultracytochemical demonstration of monoamine oxidase activity in nervous and non-nervous tissues of the rat. J Histochem Cytochem 25:337–348CrossRefGoogle Scholar
  13. Owman C (1964) Sympathetic nerves probably storing two types of monoamines in the rat pineal gland. Int J Neuropharmacol 2:105–112CrossRefGoogle Scholar
  14. Pelayo F, Dubocovich ML, Langer SZ (1977) Regulation of noradrenaline release in the rat pineal through a negative feedback mechanism mediated by presynaptic α-adrenoceptors. Eur J Pharmacol 45:317–318CrossRefGoogle Scholar
  15. Pelayo F, Dubocovich ML, Langer SZ (1978) Possible role of cyclic nucleotides in regulation of noradrenaline release from rat pineal through presynaptic adrenoceptors. Nature 274:76–78CrossRefGoogle Scholar
  16. Quay WB, Halevy A (1962) Experimental modification of the rat pineal's content of serotonin and related indoleamines. Physiol Zool 35:1–7CrossRefGoogle Scholar
  17. Racké K, Muscholl E (1986) Release of endogenous 3,4-dihydroxyphenylethylamine and its metabolites from the isolated neurointermediate lobe of the rat pituitary gland. Effects of electrical stimulation and of inhibition of monoamine oxidase and reuptake. J Neurochem 46:745–752CrossRefGoogle Scholar
  18. Racké K, Krupa H, Schröder H, Vollrath L (1989) In vitro synthesis of dopamine and noradrenaline in the isolated rat pineal gland. Day-night variations and effects of electrical stimulation. J Neurochem 53:354–361CrossRefGoogle Scholar
  19. Sommer M, Burns F, Racké K (1989) Characterization of the release of endogenous 5-hydroxytryptamine (5-HT) and noradrenaline (NA) from the rat pineal gland. Br J Pharmacol 97:459PGoogle Scholar
  20. Starke K, Göthert M, Kilbinger H (1989) Modulation of neurotransmitter release by presynaptic autoreceptors. Physiol Rev 69:864–989CrossRefGoogle Scholar
  21. Tallarida RJ, Murray RB (1981) Manual of pharmacological calculations. Springer, Berlin Heidelberg New YorkCrossRefGoogle Scholar
  22. Taranger MA, Galzin AM, Langer SZ (1987) Methiothepin enhances the potassium-evoked release of [3H]-noradrenaline in rat pineal gland. Naunyn-Schmiedeberg's Arch Pharmacol 336:374–380CrossRefGoogle Scholar
  23. Verbeuren TJ (1989) Synthesis, storage, release and metabolism of 5-hydroxytryptamine in peripheral tissues. In: Fozard JR (ed) The peripheral action of 5-hydroxytryptamine. Oxford University Press, Oxford New York Tokyo, pp 1–25Google Scholar
  24. Wallenstein S, Zucker CL, Fleiss JL (1980) Some statistical methods useful in circulation research. Circ Res 47:1–9CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • K. Racké
    • 1
  • M. Sommer
    • 1
  • F. Burns
    • 1
  • B. Hering
    • 1
  1. 1.Pharmakologisches Institut der Universät MainzMainzGermany

Personalised recommendations