A point mutation of the alpha 2-adrenoceptor that blocks coupling to potassium but not calcium currents.
The alpha 2A-adrenergic receptor (adrenoceptor) was stably expressed in AtT20 mouse pituitary tumor cells; adrenoceptor agonists inhibited adenylyl cyclase, inhibited voltage-dependent calcium currents, and increased inwardly rectifying potassium currents. An aspartic acid residue (Asp79) highly conserved among guanine nucleotide-binding protein (G protein)-coupled receptors was mutated to asparagine; in cells transfected with the mutant alpha 2-receptor, agonists inhibited adenylyl cyclase and calcium currents but did not increase potassium currents. Because distinct G proteins appear to couple adrenoceptors to potassium and calcium currents, the present findings suggest that the mutant alpha 2-adrenoceptor cannot achieve the conformation necessary to activate G proteins that mediate potassium channel activation.
Vollum Institute, Oregon Health Sciences University, Portland 97201.
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Surprenant
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Horstman
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Akbarali
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LE
Limbird
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001216:Asparagine; D001224:Aspartic Acid; D000068438:Brimonidine Tartrate; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D003000:Clonidine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D016297:Mutagenesis, Site-Directed; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D017481:Receptors, Somatostatin; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection
D000316:Adrenergic alpha-Agonists; D015220:Calcium Channels; D015221:Potassium Channels; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D011994:Recombinant Proteins; D001224:Aspartic Acid; D000068438:Brimonidine Tartrate; D013004:Somatostatin; D001216:Asparagine; D019204:GTP-Binding Proteins; D003000:Clonidine