Cyclic AMP stimulates Ca2+ entry in rat hepatocytes by interacting with the plasma membrane carriers involved in receptor-mediated Ca2+ influx.
The regulation of Ca2+ influx in rat hepatocytes by glucagon and cyclic AMP (cAMP) was investigated. Exposing hepatocytes to glucagon resulted in an increase in the initial rate of Ca2+ entry. The concentrations of glucagon producing half-maximal and maximal stimulation of Ca2+ entry were 10(-10) and 10(-8) M, respectively. A similar stimulation of Ca2+ influx was obtained in cells exposed to cAMP analogues or to forskolin. Exposing hepatocytes suspended in nominally Ca(2+)-free medium to glucagon for 3 min produced a 9% decrease in the size of the vasopressin-sensitive Ca2+ pool; in contrast, N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (Bt2cAMP) slightly augmented the size of this pool. Glucagon and Bt2cAMP synergized the initial vasopressin-stimulated Ca2+ and Mn2+ influx rates, but only moderately increased the initial rate of Ca2+ entry after thapsigargin addition. The glucagon- and Bt2cAMP-stimulated Ca2+ influx was inhibited by the same antagonists of the plasma membrane Ca2+ carriers that mediate Ca2+ entry during stimulation by vasopressin. Thus, cAMP does not stimulate Ca2+ entry through either a capacitative type of mechanism or inositol phosphate turnover. The authors' findings instead suggest that cAMP acts directly, or through protein kinase A on the same Ca2+ carriers that are activated by phospholipase C-linked receptor agonists.
Kass
G E
GE
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Gahm
A
A
Llopis
J
J
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D011956:Receptors, Cell Surface; D014667:Vasopressins; D005934:Glucagon; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium