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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adrenergic alpha-Agonists / pharmacology
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Animals
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Asparagine
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Aspartic Acid
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Brimonidine Tartrate
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Calcium Channels / drug effects
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Calcium Channels / metabolism
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Calcium Channels / physiology*
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Cell Line
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Clonidine / pharmacology
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GTP-Binding Proteins / metabolism
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Membrane Potentials / drug effects
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Mutagenesis, Site-Directed*
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Potassium Channels / drug effects
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Potassium Channels / metabolism
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Potassium Channels / physiology*
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Quinoxalines / pharmacology
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Receptors, Adrenergic, alpha / drug effects
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Receptors, Adrenergic, alpha / metabolism
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Receptors, Adrenergic, alpha / physiology*
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Receptors, Neurotransmitter / drug effects
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Receptors, Neurotransmitter / physiology*
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Receptors, Somatostatin
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Recombinant Proteins / drug effects
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Recombinant Proteins / metabolism
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Somatostatin / metabolism
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Somatostatin / pharmacology
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Transfection
Substances
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Adrenergic alpha-Agonists
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Calcium Channels
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Potassium Channels
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Quinoxalines
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Receptors, Adrenergic, alpha
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Receptors, Neurotransmitter
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Receptors, Somatostatin
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Recombinant Proteins
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Aspartic Acid
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Brimonidine Tartrate
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Somatostatin
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Asparagine
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GTP-Binding Proteins
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Clonidine