Glucagon receptor mediates calcium signaling by coupling to G alpha q/11 and G alpha i/o in HEK293 cells.
Glucagon induces intracellular Ca(2+) ([Ca(2+)](i)) elevation by stimulating glucagon receptor (GCGR). Such [Ca(2+)](i) signaling plays important physiological roles, including glycogenolysis and glycolysis in liver cells and the survival of beta-cells. Previous studies indicated that phospholipase C (PLC) might be involved in glucagon-mediated [Ca(2+)](i) response. Other studies also debated whether cAMP accumulation mediated by GCGR/G alpha(s) coupling contributes to [Ca(2+)](i) elevation. But the exact mechanisms remain uncertain. In the present study, we found that glucagon induces [Ca(2+)](i) elevation in HEK293 cells expressing GCGR. Removing extracellular Ca(2+) did not affect glucagon-stimulated [Ca(2+)](i) response. But depleting the intracellular Ca(2+) store by thapsigargin completely inhibited glucagon-induced [Ca(2+)](i) response. Experiments with forskolin and adenylyl cyclase inhibitor revealed that cAMP is not the cause of [Ca(2+)](i) response. Further studies with G alpha(q/11) RNAi and pertussis toxin (PTX) indicated that both G alpha(q/11) and G alpha(i/o) are involved. Combination of G alpha(q/11) RNAi and G alpha(i/o) inhibition almost completely abolished glucagon-induced [Ca(2+)](i) signaling.
Xu
Yazhen
Y
State Key Laboratory for Drug Research, National Center for Drug Screening, Shanghai, China.
Xie
Xin
X
D002118:Calcium / Q000819:agonists / Q000378:metabolism*; D020013:Calcium Signaling; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D037342:Pertussis Toxin / Q000494:pharmacology; D034622:RNA Interference / Q000502:physiology; D018027:Receptors, Glucagon / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019284:Thapsigargin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018027:Receptors, Glucagon; D005576:Colforsin; D019284:Thapsigargin; D005934:Glucagon; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D002118:Calcium