Dopamine Autoreceptor Stimulation Increases Protein Carboxyl Methylation in Striatal Slices

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Abstract
The possibility that protein carboxyl methylation is involved in coupling dopamine [DA] autoreceptor stimulation to intracellular events such as inhibition of dopamine synthesis or release was investigated. The DA agonists apomorphine and TL-99 [6,7-dihydro-N,N-dimethyl-2-amino-tetraline] stimulated methyl ester formation in [rat] striatal slices preloaded with [3H]methionine. The stimulatory effects of apomorphine were dose-dependent, were not due to changes in [3H]methionine uptake or S-[3H]-adenosylmethionine formation, and were blocked by the stereospecific DA antagonist (+)-butaclamol. Stimulation of methyl ester formation by DA agonists is readily observed only when slices are prepared from rats pretreated with reserpine to deplete endogenous brain catecholamines. In slices prepared from normal rats endogenous DA released during slice preparation and incubation masks the effects produced by exogenously administered DA agonists on protein carboxyl methylase (PCM) activity. The effects of apomorphine were mediated via an interaction with DA autoreceptors rather than with postsynaptic DA receptors. Destruction of monoamine neurons and their associated autoreceptors by injecting 6-hydroxydopamine into the area of the medial forebrain bundle abolished the stimulatory effects of apomorphine on methyl ester formation in striatal slices. Furthermore the putative selective DA autoreceptor agonist EMD 23 448 [3[4-(-phenyl-1,2,36-tetrahydropyrid-1-yl) butyl]indole] also stimulated methyl ester formation in striatal slices. PCM may be a key component in the biochemical transduction of DA autoreceptor stimulation.