A Point Mutation of the α_2-Adrenoceptor That Blocks Coupling to Potassium But Not Calcium Currents
Abstract
The α2A-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 α_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 α_2-adrenoceptor cannot achieve the conformation necessary to activate G proteins that mediate potassium channel activation.
- Publication:
-
Science
- Pub Date:
- August 1992
- DOI:
- 10.1126/science.1354394
- Bibcode:
- 1992Sci...257..977S