CYCLIC-AMP STIMULATES CA2-MEMBRANE CARRIERS INVOLVED IN RECEPTOR-MEDIATED CA2+ INFLUX( ENTRY IN RAT HEPATOCYTES BY INTERACTING WITH THE PLASMA)

The regulation of Ca2+ influx in rat hepatocytes by glucagon and cycli c AMP (cAMP) was investigated. Exposing hepatocytes to glucagon result ed in an increase in the initial rate of Ca2+ entry. The concentration s of glucagon producing half-maximal and maximal stimulation of Ca2+ e ntry were 10(-10) and 10(-8) M, respectively. A similar stimulation of Ca2+ influx was obtained in cells exposed to cAMP analogues or to for skolin. Exposing hepatocytes suspended in nominally Ca2+-free medium t o glucagon for 3 min produced a 9% decrease in the size of the vasopre ssin-sensitive Ca2+ pool; in contrast, N-6,2'-O-dibutyryladenosine 3': 5'-cyclic monophosphate (Bt(2)cAMP) slightly augmented the size of thi s pool. Glucagon and Bt,cAMP synergized the initial vasopressin-stimul ated Ca2+ and Mn2+ influx rates, but only moderately increased the ini tial rate of Ca2+ entry after thapsigargin addition. The glucagon- and Bt(2)cAMP-stimulated Ca2+ influx was inhibited by the same antagonist s of the plasma membrane Ca2+ carriers that mediate Ca2+ entry during stimulation by vasopressin. Thus, cAMP does not stimulate Ca2+ entry t hrough either a capacitative type of mechanism or inositol phosphate t urnover. The authors' findings instead suggest that cAMP acts directly , or through protein kinase A on the same Ca2+ carriers that are activ ated by phospholipase C-linked receptor agonists.