Cellular and subcellular localization

The distribution of receptors tells us where agonists and antagonists given to the intact organism may act. Furthermore, the rather low levels of endogenous adenosine present under basal physiological conditions have the potential of activating receptors where they are abundant, but not where they are sparse (Kenakin 1993,1995; Svenningsson etal. 1999c; Fredholm etal. 2001).

There is much information on the distribution of the A1 and A2A receptors because good pharmacological tools including radioligands are available. Several studies have used antibodies to demonstrate the widespread distribution of adenosine A1 and A2A receptors in the brain. This includes regions such as the cerebral cortex, cerebellum hippocampus, with A2a receptors being particularly enriched in the striatum (Swanson et al. 1995; Rosin et al. 1998; Hettinger et al. 2001). In the case of the A2b and A3 receptors the data are less impressive and one needs to primarily rely mRNA expression data. Some of this information is summarized in Table 11.1.

Although receptor protein and the corresponding mRNA message are in general co-localized, there are some important differences. For example, in several regions of the central nervous system, receptor binding and expression of mRNA transcripts do not exactly match (Johansson etal. 1993 a), and the two are differently regulated by long-term antagonist treatment (Johansson et al. 1993a) and during development (Aden et al. 2000). Much of the differential distribution can probably be explained by the fact that a substantial number of adenosine A1 receptors are present at nerve terminals. A similar explanation probably underlies the observations that A2A receptors are present in globus pallidus, despite the fact that A2a receptor mRNA cannot be detected there (Svenningsson et al. 1997, 1999c). These receptors are probably located at the terminals of the striatopallidal GABAergic neurons (Rosin etal. 1998; Svenningsson etal. 1999b; Linden 2001).

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