Summary
The third ventricle and the aqueduct of anaesthetized cats were cannulated and the posterior area of the hypothalamus was stimulated with a monopolar electrode. Electrical stimulation of the posterior area evoked a rise of the arterial blood pressure which was inhibited by the injection of 0.2 ml of gammaaminobutyric acid (GABA, 2M) into the third ventricle. The impairment of the pressor response to electrical stimulation was accompanied by a fall of the “resting” blood pressure and depression of the respiration, presumably by action of GABA on brain areas in the vicinity of the fourth ventricle. In another series of experiments the posterior area was labelled with (±)-3H-noradrenaline and 2 h later superfused with a push-pull cannula and stimulated with the tip of the cannula. Superfusion with GABA (0.1 or 1 M) evoked a dose-dependent increase of release of catecholamines and enhanced the pressor response to electrical stimulation. 1×10−3 M of GABA enhanced the pressor response without increasing the spontaneous release of catecholamines but potentiated the output of radioactivity during electrical stimulation. Superfusion with sucrose (1 M) did not influence either pressor response or release of radioactive compounds. Superfusion with GABA increased slightly but significantly the relative concentration of catechols in the effluents and reduced that of normetanephrine. Pretreatment of animals with pargyline and tropolone evoked a pronounced increase of the relative concentrations of catechols in the effluent, while those of 3-methoxy-4-hydroxyphenylglycol and 3-methoxy-4-hydroxymandelic acid were strongly reduced. It is concluded that superfusion with high concentrations of GABA enhances the pressor response by increasing the release of catecholamines, while the effect of low GABA concentrations is due to facilitation of release of catecholamines from the adrenergic nerve endings during electrical stimulation.
Similar content being viewed by others
References
Bhargava, K. P., Bhattacharya, S. S., Srimal, R. C.: Central cardiovascular actions of gamma-aminobutyric acid. Brit. J. Pharmacol. 23, 383–390 (1964).
Crout, R.: Catechol amines in urine. In: Standard methods of clinical Chemistry, vol. 1, pp. 62–80, New York: Academic Press 1961.
DeFeudis, F. V., Delgada, J. M. R., Roth, R. H.: Content, synthesis and collectability of aminoacids in various structures of the brains of rhesus monkeys. Brain Res. 18, 15–23 (1970).
Elliott, K. A. C., Hobbiger, F.: Gamma-aminobutyric acid: circulatory and respiratory effects in different species; re-investigation of the anti-strychnine action in mice. J. Physiol. (Lond.) 146, 70–84 (1959).
Folkow, B., Rubinstein, E. H.: Cardiovascular effects of acute and chronic stimulation of the hypothalamus defense area in rat. Acta physiol. scand. 68, 48–57 (1966).
Gelder, M. M. v., Elliott, K. A. C.: Distribution of gamma-aminobutyric acid administered to animals. J. Neurochem. 3, 139–142 (1958).
Javoy, F., Hamon, M., Glowinski, J.: Disposition of newly synthesized amines in cell bodies and terminals of central catechol aminergic neurons. (I) Effect of amphetamine and thioproperazine on the metabolism of CA in the caudate nucleus, the substantia nigra and the ventromedial nucleus of the hypothalamus. Europ. J. Pharmacol. 10, 178–188 (1970).
Karplus, J. P., Kreidl, A.: Gehirn und Sympathieus. VII. Über Beziehungen der Hypothalamuszentren zu Blutdruck und innerer Sekretion. Pflügers Arch. ges. Physiol. 215, 667–670 (1927).
Kopin, I., Axelrod, J., Gordon, E.: The metabolic fate of epinephrine-3H and metanephrine-14C. J. biol. Chem. 236, 2109–2113 (1961).
Magoun, H. W.: Excitability of the hypothalamus after degeneration of cortifugal connections from the frontal lobes. Amer. J. Physiol. 122, 530–532 (1938).
Merlis, J. K.: The effect of changes in the calcium content of cerebrospinal fluid on spinal reflex activity in the dog. Amer. J. Physiol. 13, 67–72 (1940).
Philippu, A., Heyd, G., Burger, A.: Release of noradrenaline from the hypothalamus in vivo. Europ. J. Pharmacol. 9, 52–58 (1970).
Philippu, A., Przuntek, H., Heyd, G., Burger, A.: Central effects of sympathomimetic amines on the blood pressure. Europ. J. Pharmacol. 15, 200–208 (1971).
Przuntek, H., Guimaraes S., Philippu, A.: Importance of adrenergic neurons of the brain for the rise of blood pressure evoked by hypothalamic stimulation. Naunyn-Schmiedebergs Arch. Pharmak. 271, 311–319 (1971).
Reinoso-Suarez, F.: Topographischer Hirnatlas der Katze. Darmstadt: Merck AG 1961.
Strasberg, P., Krnjevic, K., Schwartz, S., Elliott, K. A. C.: Penetration of bloodbrain barrier by gamma-aminobutyric acid at sites of freezing. J. Neurochem. 14, 755–760 (1967).
Winne, D.: Zur Auswertung von Versuchsergebnissen: die Prüfung, ob Kurven sich in ihrem Verlauf unterscheiden. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 250, 383–396 (1965).
Yessaian, N. H., Armenian, A. R., Buniatian, H. Ch.: Effect of gamma-aminobutyric acid on brain serotonin and catecholamines. J. Neurochem. 16, 1425–1433 (1969).
Author information
Authors and Affiliations
Additional information
This work was supported by the Deutsche Forschungsgemeinschaft and the Stiftung Volkswagenwerk.
Rights and permissions
About this article
Cite this article
Philippu, A., Przuntek, H. & Roensberg, W. Superfusion of the hypothalamus with gamma-aminobutyric acid. Naunyn-Schmiedeberg's Arch. Pharmacol. 276, 103–118 (1973). https://doi.org/10.1007/BF00501183
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00501183