The effects of pertussis toxin on autoreceptor-mediated inhibition of dopamine synthesis in the rat striatum.
Activation of synthesis-modulating dopamine autoreceptors by dopamine or its agonists has been shown to inhibit dopamine synthesis in the rat striatum. However, systemic administration of the direct-acting dopamine agonist apomorphine failed to inhibit dopamine synthesis in striata from rats that had received local unilateral administration of pertussis toxin. Apomorphine did reduce dopamine synthesis by greater than 50% in sham injected control rats as well as in the striata opposite to the side of pertussis toxin injection. Examination of G proteins in striatal tissue revealed that 61% of the G proteins were ADP-ribosylated in vivo by direct pertussis toxin injection. These data suggest that guanine nucleotide regulatory proteins mediate the effects of activation of striatal synthesis-modulating dopamine autoreceptors.
Bean
A J
AJ
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut.
Shepard
P D
PD
Bunney
B S
BS
Nestler
E J
EJ
Roth
R H
RH
D015107:4-Butyrolactone / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D006834:Hydrazines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D004295:Dihydroxyphenylalanine; C004297:3-hydroxybenzylhydrazine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D001058:Apomorphine; D015107:4-Butyrolactone; D004298:Dopamine