title: Neurochemical and behavioural evidence that dopamine D-2 receptors in striatum couple to the Ni regulatory protein and inhibition of cyclic AMP accumulation.
abstract: 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.
authors.forename: E
authors.initials: E
authors.lastname: Kelly
authors.forename: A L
authors.initials: AL
authors.lastname: Willcocks
authors.forename: S R
authors.initials: SR
authors.lastname: Nahorski
mesh_terms: 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*
chemical_list: 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