Gene encoding the rat dopamine D.sub.4 receptor

Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...

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435 721, 4352523, 435325, 536 231, C12P 2106

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061210153

ABSTRACT:
A gene, flanking 5' and 3' sequences and derived cDNA encoding a rat D.sub.4 dopamine receptor that is predominantly located in the cardiovascular and retinal systems is disclosed. The cDNA has been expressed in transfected mammalian cells and demonstrated to preferentially bind dopamine antagonists such as clozapine. The cDNA is useful as a probe for related D.sub.4 dopamine receptors. Expressed in appropriate cell lines, it is useful as an in vitro screen for drugs which specifically bind to the receptor. Drugs that specifically bind to the receptor are then screened using standard methodology in rats, mice or dogs, for the physiological effects. Amino acids deduced from the determination of cDNA can be used to generate either polyclonal or monoclonal antibodies which recognize the D.sub.4 receptor sequence but do not recognize D.sub.1, D.sub.2, D.sub.3 or D.sub.5 dopamenergic receptors, for use in immunocytochemical studies, and for identification and isolation via flow sorting of D4 expressing cell types. Antibodies could also be used to block or modify the effects of D4 agonists and/or antagonists. It is also demonstrated that selective stimulation or inhibition of some dopamine receptors, including D.sub.4, can be used to induce changes in the morphology of cells such as neurons.

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