D2 but not D1 dopamine receptor stimulation augments brain signaling involving arachidonic acid in unanesthetized rats.
OBJECTIVE
Signal transduction involving the activation of phospholipase A2 (PLA2) to release arachidonic acid (AA) from membrane phospholipids, when coupled to dopamine D1- and D2-type receptors, can be imaged in rats having a chronic unilateral lesion of the substantia nigra. It is not known, however, if the signaling responses occur in the absence of a lesion. To determine this, we used our in vivo fatty acid method to measure signaling in response to D1 and D2 receptor agonists given acutely to unanesthetized rats.


METHODS
[1-(14)C]AA was injected intravenously in unanesthetized rats, and incorporation coefficients k* for AA (brain radioactivity/integrated plasma radioactivity) were measured using quantitative autoradiography in 61 brain regions. The animals were administered i.v. the D2 receptor agonist, quinpirole (1 mg kg(-1), i.v.), the D1 receptor agonist SKF-38393 (5 mg kg(-1), i.v.), or vehicle/saline.


RESULTS
Quinpirole increased k* significantly in multiple brain regions rich in D2-type receptors, whereas SKF-38393 did not change k* significantly in any of the 61 regions examined.


CONCLUSIONS
In the intact rat brain, D2 but not D1 receptors are coupled to the activation of PLA2 and the release of AA.
Bhattacharjee
Abesh Kumar
AK
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bldg. 9, Room 1S128, Bethesda, MD 20892, USA. abeshb@mail.nih.gov
Chang
Lisa
L
Lee
Ho-Joo
HJ
Bazinet
Richard P
RP
Seemann
Ruth
R
Rapoport
Stanley I
SI
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism* / Q000493:pharmacokinetics; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D018491:Dopamine Agonists / Q000494:pharmacology; D004333:Drug Administration Routes; D004347:Drug Interactions; D008297:Male; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014851:Wakefulness
D002247:Carbon Isotopes; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D016718:Arachidonic Acid; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine