Dopamine autoreceptor stimulation increases protein carboxyl methylation in striatal slices.
We have investigated the possibility that protein carboxyl methylation is involved in coupling dopamine autoreceptor stimulation to intracellular events such as inhibition of dopamine synthesis or release. The dopamine agonists apomorphine and TL-99 were found to stimulate methyl ester formation in 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 dopamine antagonist (+)-butaclamol. Stimulation of methyl ester formation by dopamine agonists is readily observed only when slices are prepared from rats pretreated with reserpine to deplete endogenous brain catecholamines. This suggests that in slices prepared from normal rats endogenous dopamine (DA) released during slice preparation and incubation masks the effects produced by exogenously administered dopamine agonists on protein carboxyl methylase (PCM) activity. Additional experiments suggested that 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 was also found to stimulate methyl ester formation in striatal slices. These findings, discussed in terms of calcium-dependent functions, support the hypothesis that PCM may be a key component in the biochemical transduction of DA autoreceptor stimulation.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008715:Methionine / Q000378:metabolism; D011496:Protein Methyltransferases / Q000378:metabolism*; D011497:Protein O-Methyltransferase / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D012110:Reserpine / Q000494:pharmacology; D013997:Time Factors
D007211:Indoles; D011954:Receptors, Dopamine; C037307:3-(4-(4-phenyl-1,2,3,6-tetrahydropyridyl-1)-butyl)indole; D012110:Reserpine; D008715:Methionine; D011496:Protein Methyltransferases; D011497:Protein O-Methyltransferase; D001058:Apomorphine