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  • Title: A point mutation of the alpha 2-adrenoceptor that blocks coupling to potassium but not calcium currents.
    Author: Surprenant A, Horstman DA, Akbarali H, Limbird LE.
    Journal: Science; 1992 Aug 14; 257(5072):977-80. PubMed ID: 1354394.
    Abstract:
    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.
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