Neurochemical and behavioural evidence that dopamine D-2 receptors in striatum couple to the Ni regulatory protein and inhibition of cyclic AMP accumulation.
The effects of intrastriatal pertussis toxin, which inactivates the regulatory protein Ni, were investigated in various models of striatal D-2 receptor function in the rat. Using a multiple injection technique unilateral intrastriatal injections of pertussis toxin induced, after a lag phase, ipsilateral postural asymmetries which intensified upon peripheral administration of apomorphine. Injections of pertussis toxin also partially reduced the ability of a selective D-2 agonist, RU 24926 [N-n-propyl di-beta (3-hydroxyphenyl)-ethylamine], to inhibit cyclic AMP accumulation due to a selective D-1 agonist SKF 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine), whilst also reducing the affinity of dopamine for D-2 binding sites in striatal membranes from animals given prior intrastriatal injections of the toxin. Pertussis toxin also increased striatal dopamine metabolism, seen as a reduction in the dopamine: DOPAC (3,4-Dihydroxyphenylacetic acid) ratio, similar to that seen following intrastriatal injections of the selective D-2 antagonist (+/-)-sulpiride. These results suggest that pertussis toxin has dopamine D-2 antagonist-like properties in the rat striatum, consistent with the idea that striatal D-2 function may rely, in part at least, upon the regulatory protein Ni and adenylate cyclase inhibition.
Kelly
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Willcocks
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Nahorski
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D037361:Adenylate Cyclase Toxin; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D001552:Benzazepines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D010566:Virulence Factors, Bordetella; D013134:Spiperone; D013469:Sulpiride; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D001058:Apomorphine; D004298:Dopamine