Alpha 2-adrenergic receptor stimulation of phospholipase A2 and of adenylate cyclase in transfected Chinese hamster ovary cells is mediated by different mechanisms.
The effect of alpha 2-adrenergic receptor activation on adenylate cyclase activity in Chinese hamster ovary cells stably transfected with the alpha 2A-adrenergic receptor gene is biphasic. At lower concentrations of epinephrine forskolin-stimulated cyclic AMP production is inhibited, but at higher concentrations the inhibition is reversed. Both of these effects are blocked by the alpha 2 antagonist yohimbine but not by the alpha 1 antagonist prazosin. Pretreatment with pertussis toxin attenuates inhibition at lower concentrations of epinephrine and greatly potentiates forskolin-stimulated cyclic AMP production at higher concentrations of epinephrine. alpha 2-Adrenergic receptor stimulation also causes arachidonic acid mobilization, presumably via phospholipase A2. This effect is blocked by yohimbine, quinacrine, removal of extracellular Ca2+, and pretreatment with pertussis toxin. Quinacrine and removal of extracellular Ca2+, in contrast, have no effect on the enhanced forskolin-stimulated cyclic AMP production. Thus, it appears that the alpha 2-adrenergic receptor in these cells can simultaneously activate distinct signal transduction systems; inhibition of adenylate cyclase and stimulation of phospholipase A2, both via G1, and potentiation of cyclic AMP production by a different (pertussis toxin-insensitive) mechanism.
Jones
S B
SB
Department of Pharmacology, School of Medicine, University of Missouri-Columbia 65212.
Halenda
S P
SP
Bylund
D B
DB
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000096:biosynthesis; D004789:Enzyme Activation; D005260:Female; D007700:Kinetics; D008566:Membranes / Q000378:metabolism; D010053:Ovary / Q000166:cytology; D037342:Pertussis Toxin; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D011224:Prazosin / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013268:Stimulation, Chemical; D013997:Time Factors; D014162:Transfection; D014316:Tritium; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D015016:Yohimbine / Q000378:metabolism
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D014316:Tritium; D005576:Colforsin; D015016:Yohimbine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D010741:Phospholipases A; D054467:Phospholipases A2; D000262:Adenylyl Cyclases; D011796:Quinacrine; D011224:Prazosin