Cortex mouse brain

Figure 21.2 Mass spectra obtained from the cerebral cortex region (a) of mouse brain. Signals with good S/N ratios were obtained from thin slices. Modifed with permission from Sugiura et al.3...

In a cooperation project20 with Professor H. Timmerman, Dr. R. Leurs and coworkers (Vrije Universiteit Amsterdam), we compared the effects of the higher homologues of histamine (i.e. replacement of the ethylene side chain by n-propylene, n-butylene, n-pentylene etc.) in mouse brain cortex slices and in guinea-pig jejunum. 

Fig. 4. Schematic drawing of an axon terminal of the noradrenergic neurone in the mouse brain cortex. The axon terminal is endowed with several types of presynaptic receptors including the autoreceptor for noradrenaline itself (which is an a2D-adrenoceptor in this species45) and a variety of heteroreceptors (only the H3 and EP3 heteroreceptors are identified).

Schlicker E, Behling A, Liimmen G, Gothert M (1992) Histamine H3A receptor-mediated inhibition of noradrenaline release in the mouse brain cortex. Naunyn-Schmiedeberg s Arch Pharmacol 345 489-493. 

Schlicker E, Kathmann M, Bitschnau H, Marr I, Reidemeister S, Stark H, Schunack W (1996) Potencies of antagonists chemically related to iodoproxyfan at histamine H3 receptors in mouse brain cortex and guinea-pig ileum evidence for H3 receptor heterogeneity Naunyn-Schmiedeberg s Arch Pharmacol 353 482-488. 

An important criterion for the identification of receptor subtypes is that they are related to distinct functional responses. Based on the functional potencies of thioperamide and of tiotidine, H3A- and H3B-receptors were suggested to be linked to H3-receptor mediated inhibition of histamine release and synthesis, respectively (West et al., 1990b). At present, not much additional evidence for this suggestion has been presented. Histamine H3-receptors inhibiting noradrenaline release in mouse brain cortex slices have been suggested to represent the H3A-receptor subtype (Schlicker et al., 1992 Schlicker et al., 1994). To our knowledge, functional responses in brain tissue related to the g-receptor have never been observed however. 

Fig. 3 Autoreceptor versus heteroreceptor functions of a2-adrenoceptor subtypes, (a and b) Inhibition of electrically evoked [3H]-adrenaline release by the 012-agonist, medetomidine, from mouse brain cortex (a) or heart atria (b). In wild-type tissue specimens, medetomidine inhibited transmitter release by >90%. In tissues from a2AC-deficient mice, the agonist effect was absent (a, cortex) or significantly reduced (b, atria). Reproduced with permission from Trendelenburg et al. 2003b. (c) Overview of auto- and heteroreceptor functions of a2-adrenoceptor subtypes. For references, see text.

Figure 4 shows how a presynaptic neuropeptide Y receptor was identified in a superfusion model. In mouse brain cortex slices, serotonin release was concentration-dependently inhibited by neuropeptide Y and this effect was potently mimicked by neuropeptide Y-(13-36). Since the latter is selective for Y2 over Yi andYs receptors (Alexander et al. 2006) one may conclude that neuropeptide Y acts via Y2 receptors. 

Fig. 4 Effect of various peptides and nonpeptides on the electrically (3 Hz) evoked tritium overflow from superfused mouse brain cortex slices preincubated with 3H-serotonin. The evoked overflow represents quasi-physiological exocytotic serotonin release. In all experiments, serotonin autoreceptors were blocked by metitepine. The figure shows that human neuropeptide Y concentration-dependently inhibited serotonin release and that this effect was mimicked by human neuropeptide Y (13-36) (NPYi3 36), which has a high affinity for Y2 but a very low affinity for Yi receptors. These results are compatible with the view that neuropeptide Y acts via Y2 receptors in the present model. For the sake of comparison, the figure also shows the inhibitory effects of another three agonists, acting via cannabinoid CBi, histamine H3 and prostaglandin EP3 receptors and used at concentrations causing the maximum or near-maximum effect at their respective receptors. Drug concentrations in pM. P < 0.05, P < 0.003, compared to the control (from Nakazi et al. 2000 and Nakazi 2001 redrawn).

The D4 receptor has been described in layers II-VI of both the frontal and the piriform cortex of the mouse brain, with the highest concentration in layer II. D4 receptors are distributed in somata and proximal processes of pyramidal neurons. In cortical regions, the levels of D4 receptors were found to be higher than those of D2 and D3 receptors (Ariano et al., 1997 Mauger et al., 1998). 

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