Increased abundance of alternatively spliced forms of D2 dopamine receptor mRNA after denervation

K. A. Neve, R. L. Neve, S. Fidel, A. Janowsky, G. A. Higgins

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Abstract

The existence of two molecular forms of D2 dopamine receptors suggests that differences in the distribution or regulation of the two forms could be exploited for the pharmacological treatment of disease. Using probes selective for each alternatively spliced variant of D2 receptor mRNA, we determined that both variants were widely distributed in rat brain and pituitary but that the ratio of the forms varied among regions. mRNA for the 444-amino acid-long variant, D2444, was the most abundant form in pituitary and neostriatum. Intermediate levels of both D2444 mRNA and the short form, D2415, were detected in midbrain, and low levels of D2444 and D2415 mRNAs were detected in all other regions examined, including hippocampus, cerebellum, and cortex. The D2444/D2415 ratio was generally lower in the regions of low expression than in pituitary and neostriatum. Dopamine-depleting lesions increased the density of D2 receptors in the denervated neostriatum by 29% without altering the affinity of the receptors for [3H]spiperone. The proliferation of receptors appeared to be due to a lesion-induced increase of up to 120% in the abundance of both variants of mRNA in the neostriatum.

Original languageEnglish (US)
Pages (from-to)2802-2806
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number7
DOIs
StatePublished - Jan 1 1991

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