Characterization of dopamine and beta-adrenergic receptors linked to cyclic AMP formation in intact cells of the clone D384 derived from a human astrocytoma.
3,4-Dihydroxyphenylethylamine (dopamine) and beta-adrenergic receptor agonists and antagonists were assessed for their effects on cyclic AMP accumulation in human astrocytoma derived clone D384 cells. Dopamine, SKF 38393, and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene increased cyclic AMP content with Ka values of 2.0, 0.2, and 1.6 microM. The D1-selective antagonists SCH 23390 (Ki, 1.2 nM) and SKF 83566 (Ki, 0.8 nM) were over 5,000-fold more potent than the D2-selective antagonist domperidone (Ki, 6.7 microM) at inhibiting dopamine stimulation of cyclic AMP formation. SCH 23388 (Ki, 560 nM; the S-enantiomer of SCH 23390) was 400-fold less potent than SCH 23390. Isoprenaline, adrenaline, salbutamol, and noradrenaline increased cyclic AMP content with Ka values of 0.13, 0.12, 0.22, and 7.60 microM. The beta 2-selective antagonist ICI 118,551 (Ki,0.8 nM) was almost 8,000-fold more potent than the beta 1-selective antagonist practolol (Ki, 5.9 microM) at inhibiting isoprenaline stimulated cyclic AMP accumulation. These results demonstrate that D384 cells express D1-dopamine and beta 2-adrenergic receptors linked to adenylate cyclase. Furthermore, the dopamine receptor expressed by D384 cells exhibits a pharmacological profile typical of a mammalian striatal D1-receptor and therefore the use of this clone represents another approach to studying central D1-receptors.
Balmforth
A J
AJ
M.R.C. Blood Pressure Unit, Western Infirmary, Glasgow, Scotland.
Yasunari
K
K
Vaughan
P F
PF
Ball
S G
SG
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives; D000319:Adrenergic beta-Antagonists; D001254:Astrocytoma / Q000378:metabolism*; D001552:Benzazepines / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D011217:Practolol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015056:1-Methyl-3-isobutylxanthine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D000242:Cyclic AMP; D004294:Domperidone; D004298:Dopamine; D018492:Dopamine Antagonists; D007545:Isoproterenol; D011217:Practolol; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D013764:Tetrahydronaphthalenes; C026777:ICI 118551; C011639:ADTN; C044846:SKF83566