Adrenergic agonists induce heterologous sensitization of adenylate cyclase in NS20Y-D(2L) cells.
Adenylate cyclase activity in NS20Y cells expressing D2L dopamine receptors was examined following chronic treatment with norepinephrine and epinephrine. Initial acute experiments revealed that both norepinephrine and epinephrine inhibited forskolin-stimulated cyclic AMP accumulation via D2 receptors. Furthermore, chronic 18 h activation of D2 dopamine receptors by norepinephrine or epinephrine induced a marked increase (>10-fold) in subsequent forskolin-stimulated cyclic AMP accumulation. This heterologous sensitization of adenylate cyclase activity was blocked by D2 dopamine receptor antagonists and by pertussis toxin pretreatment. In contrast, concurrent activation of Galpha(s) or adenylate cyclase did not appear to alter noradrenergic agonist-induced sensitization.
Johnston
C A
CA
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, MCMP 1333, RHPH 224A, West Lafayette, IN 47907, USA.
Cumbay
M G
MG
Vortherms
T A
TA
Watts
V J
VJ
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000322:Adrenergic Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000322:Adrenergic Agonists; D000319:Adrenergic beta-Antagonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D010566:Virulence Factors, Bordetella; C113776:dopamine D2L receptor; D005576:Colforsin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases; D009638:Norepinephrine; D004837:Epinephrine