Elsevier

Neuroscience

Volume 80, Issue 1, 25 June 1997, Pages 241-249
Neuroscience

Histamine H3 receptor activation selectively inhibits dopamine D1 receptor-dependent [3H]GABA release from depolarization-stimulated slices of rat substantia nigra pars reticulata

https://doi.org/10.1016/S0306-4522(97)00100-0Get rights and content

Abstract

The release of [3H]GABA from slices of rat substantia nigra pars reticulata induced by increasing extracellular K+ from 6 to 15 mM in the presence of 10 μM sulpiride was inhibited by 73±3% by 1 μM SCH 23390, consistent with a large component of release dependent upon D1 receptor activation. The histamine H3 receptor-selective agonist immepip (1 μM) and the non-selective agonist histamine (100 μM) inhibited [3H]GABA release by 78±2 and 80±2%, respectively. The inhibition by both agonists was reversed by the H3 receptor antagonist thioperamide (1 μM). However, in the presence of 1 μM SCH 23390 depolarization-induced release of [3H]GABA was not significantly decreased by 1 μM immepip. In rats depleted of dopamine by pretreatment with reserpine, immepip no longer inhibited control release of [3H]GABA, but in the presence of 1 μM SKF 38393, which produced a 7±1-fold stimulation of release, immepip reduced the release to a level not statistically different from that in the presence of immepip alone. Immepip (1 μM) also inhibited the depolarization-induced release of [3H]dopamine from substantia nigra pars reticulata slices, by 38±3%.

The evidence is consistent with the proposition that activation of histamine H3 receptors leads to the selective inhibition of the component of depolarization-induced [3H]GABA release in substantia nigra pars reticulata slices which is dependent upon D1 receptor activation. This appears to be largely an action at the terminals of the striatonigral GABA projection neurons, which may be enhanced by a partial inhibition of dendritic [3H]dopamine release.

Section snippets

Measurement of [3H]GABA release from slices of substantia nigra pars reticulata

Slices of substantia nigra pars reticulata (SNr) were dissected from Vibratome-cut slices (300 μm) of rat (Wistar strain, males, approximately 250 g body weight; bred in the Centro de Investigacion) brain and incubated for 20 min at 37°C in 4.5 ml of a modified Krebs–Henseleit solution (composition in mM: NaCl 134, KCl 4.75, MgSO4 1, KH2PO4 1.25, NaHCO3 25, CaCl2 2 and d-glucose 10) gassed continously with O2/CO2 (95:5, v/v). Usually eight to 10 slices of SNr were obtained from each animal. The

Potentiation by sulpiride of depolarization-induced release of [3H]GABA

The release of [3H]GABA from slices of SNr induced by increasing the K+ concentration in the superfusate from 6 to 15 mM was consistently increased by the addition of the dopamine D2 receptor antagonist sulpiride (10 μM) (Fig. 1), although the magnitude of the effect of sulpiride differed between experiments and did not reach statistical significance in one of the three experiments. Basal release of [3H]GABA was not significantly altered by 10 μM sulpiride, as determined by comparison of the

Selectivity of H3 agonist action against D1 receptor-potentiated [3H]GABA release

The results presented above demonstrate that histamine H3 receptor activation results in the inhibition of the depolarization-stimulated release of [3H]GABA from microdissected slices of rat SNr. However, the most striking finding is that H3 agonist action is directed selectively against that fraction of [3H]GABA release dependent on the activation of dopamine D1 receptors on the terminals of the striatal projection neurones. The extent to which [3H]GABA release is D1 agonist dependent[14]under

Conclusions

Depolarization-induced release of [3H]GABA from microdissected slices of rat SNr is strongly potentiated by activation of dopamine D1 receptors on the terminals of striatonigral projection neurons. Activation of histamine H3 receptors on these terminals by histamine or by the H3 agonist immepip selectively inhibits the portion of [3H]GABA release dependent on the presence of a D1 receptor agonist. This action of H3 agonists may be complemented by a partial inhibition of depolarization-induced

Acknowledgements

This work was supported by Grant 1381-PN from CONACyT (Mexico). The visit of J.M.Y. to Mexico was made under the auspices of an exchange agreement between the Royal Society of London and the Academia de la Investigacion Cientifica of Mexico.

References (37)

  • R Leurs et al.

    Molecular pharmacological aspects of histamine receptors

    Pharmac. Ther.

    (1995)
  • N Mons et al.

    Adenylate cyclases: critical foci in neuronal signaling

    Trends Neurosci.

    (1995)
  • H Pollard et al.

    Increased synthesis and release of [3H]histamine in rat brain by reserpine

    Eur. J. Pharmac.

    (1973)
  • H Pollard et al.

    A detailed autoradiographic mapping of histamine H3 receptors in rat brain areas

    Neuroscience

    (1993)
  • R.P.J.M Smits et al.

    Inhibitory effects of histamine on the release of serotonin and noradrenaline from rat brain slices

    Neurochem. Int.

    (1991)
  • J.M Arrang et al.

    Characterization of histamine H3 receptors regulating acetylcholine release in rat entorhinal cortex

    Br. J. Pharmac.

    (1995)
  • J.M Arrang et al.

    Highly potent and selective ligands for histamine H3 receptors

    Nature

    (1987)
  • J.M Arrang et al.

    Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor

    Nature

    (1983)
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