Effect of Gi protein ADP-ribosylation induced by pertussis toxin on dopamine-mediated behaviors.
The effect of Gi protein modification produced by intrastriatal pertussis toxin injection on dopamine (DA)-mediated behaviors was studied. Administration of the selective D2 agonist quinpirole induced ipsilateral rotation but the selective D1 agonist SKF 38393 did not. However, SKF 38393 was able to increase the rotation induced by quinpirole. The selective D2 antagonist raclopride and the selective D1 antagonist SCH 23390 both blocked the effect of quinpirole. Striatal levels of cAMP were measured in both intact and pertussis toxin injected striatum. SKF 38393 induced a significant increase in cAMP, but quinpirole had no effect. When both drugs were administered together, quinpirole attenuated the SKF 38393-induced increase in cAMP levels. Moreover, quinpirole-induced attenuation of SKF 38393 effect was greater in intact striatum. In pertussis toxin-injected striatum, quinpirole only attenuated SKF 38393-induced increase of cAMP to control levels. This imbalance between intact and injected striatum might be the cause of the rotation in pertussis toxin-injected rats suggesting an important role for G proteins in DA receptor interactions.
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD.
C
C
Marin
S A
SA
Parashos
T N
TN
Chase
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D037342:Pertussis Toxin; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology; D012399:Rotation; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D015259:Dopamine Agents; D004873:Ergolines; D011954:Receptors, Dopamine; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins