Dopamine D-2 receptors inhibit D-1 stimulated cyclic AMP accumulation in striatum but not limbic forebrain.
The effect of dopamine D-2 receptor activation on dopamine D-1 stimulated cyclic AMP accumulation was investigated in slices of rat striatum and limbic forebrain (nucleus accumbens and tuberculum olfactorium). In striatal slices the dose-dependent increase in cyclic AMP accumulation due to dopamine (3-100 mumol/l) was enhanced by selective D-2 receptor blockade using (-)-sulpiride (30 mumol/l). In limbic slices the increase in cyclic AMP due to dopamine (3-50 mumol/l) was unaffected by selective D-2 receptor blockade. The enhancement of cyclic AMP accumulation due to the selective D-1 agonist SKF 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; 1 mumol/l) in striatal slices was attenuated in the presence of the selective D-2 receptor agonist LY 171555 (quinpirole hydrochloride; 10 mumol/l). This attenuation was in turn blocked by (-)-sulpiride (10 mumol/l). In limbic slices LY 171555 (10 mumol/l) had no effect on SKF 38393 (1 mumol/l) stimulated cyclic AMP accumulation. Conversely muscarine receptor activation, using carbachol (10 mumol/l), attenuated D-1 stimulated cyclic AMP accumulation in both striatum and limbic forebrain. Dopamine D-2 or muscarine receptor stimulation in either striatal or limbic slices did not attenuate cyclic AMP accumulation due to VIP (vasoactive intestinal polypeptide; 0.5 mumol/l), isoprenaline (10 mumol/l) or 2-chloroadenosine (100 mumol/l). This suggests that in striatal slices, D-2 receptors mediate a selective inhibition of D-1 stimulated cyclic AMP accumulation, but that in the limbic forebrain D-2 receptors are unlikely to be coupled to D-1 receptor-linked adenylate cyclase. These data indicate a fundamental difference in the properties of D-2 receptor-effector coupling in these brain regions.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D004873:Ergolines / Q000494:pharmacology; D066298:In Vitro Techniques; D008032:Limbic System / Q000378:metabolism*; D008297:Male; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology
D001067:Appetite Depressants; D001552:Benzazepines; D004873:Ergolines; D011954:Receptors, Dopamine; D011976:Receptors, Muscarinic; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; D002217:Carbachol; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine