Additivity and non-additivity between dopamine-, norepinephrine-, carbachol- and GABA-stimulated GTPase activity.
The mode of coupling between neurotransmitter receptors and G proteins was investigated by agonist-induced high-affinity GTPase activity in rat striatal membranes. There was a simple additive relationship among dopamine-, carbachol-, and gamma-aminobutyric acid (GABA)-sensitive high-affinity GTPase activity in any combination, indicating that the respective receptors stimulated by these agonists (i.e., dopamine D2, pirenzepine-insensitive muscarinic, and GABAB receptors) interact independently with distinct pools of G proteins. Unexpectedly non-additivity was observed between dopamine- and norepinephrine-stimulation. This lack of additivity was apparently due to stimulation of the same dopamine D2 receptors by both dopamine and norepinephrine, since norepinephrine-stimulated high-affinity GTPase activity could be inhibited by dopaminergic but not adrenergic antagonists. The same non-additivity as seen in rat striatum was confirmed in the membranes prepared from cultured mouse fibroblast cells co-transfected with dopamine D2 and adenosine A2A receptors. The implication of the (non-)additivity between receptor-mediated high-affinity GTPase activity was discussed with a consideration of the possible underlying molecular mechanism.
Odagaki
Y
Y
Department of Neuroscience, Karolinska Institute, Slockholm, Sweden.
Dasgupta
S
S
Fuxe
K
K
D000322:Adrenergic Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D020558:GTP Phosphohydrolases / Q000819:agonists* / Q000378:metabolism; D007739:L Cells; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000322:Adrenergic Agonists; D000317:Adrenergic alpha-Antagonists; D018492:Dopamine Antagonists; D017981:Receptors, Neurotransmitter; D005680:gamma-Aminobutyric Acid; D002217:Carbachol; D020558:GTP Phosphohydrolases; D001418:Baclofen; D004298:Dopamine; D009638:Norepinephrine