Glucagon and vasopressin interactions on Ca2+ movements in isolated hepatocytes

Abstract

The effects of glucagon and vasopressin, singly or together, on cytosolic free Ca2+ concentration [( Ca2+]i) and on the 45Ca2+ efflux were studied in isolated rat liver cells. In the presence of 1 mM external Ca2+, glucagon and vasopressin added singly induced sustained increases in [Ca2+]i. The rate of the initial fast phase of the [Ca2+]i increase and the magnitude of the final plateau were dependent on the concentrations (50 pm-0.1 microM) of glucagon and vasopressin. Preincubating the cells with a low concentration of glucagon (0.1 nM) for 2 min markedly accelerated the fast phase and elevated the plateau of the [Ca2+]i increase caused by vasopressin. In the absence of external free Ca2+, glucagon and vasopressin transiently increased [Ca2+]i and stimulated the 45Ca2+ efflux from the cells, indicating mobilization of Ca2+ from internal store(s). Preincubating the cells with 0.1 nM-glucagon accelerated the rate of the fast phase of the [Ca2+]i rise caused by the subsequent addition of vasopressin. However, unlike what was observed in the presence of 1 mM-Ca2+, glucagon no longer enhanced the maximal [Ca2+]i response to vasopressin. In the absence of external free Ca2+, higher concentrations (1 nM-0.1 microM) of glucagon, which initiated larger increases in [Ca2+]i, drastically decreased the subsequent Ca2+ response to vasopressin (10 nM). At these concentrations, glucagon also decreased the vasopressin-stimulated 45Ca2+ efflux from the cells. It is suggested that, in the liver, glucagon accelerates the fast phase and elevates the plateau of the vasopressin-mediated [Ca2+]i increase respectively by releasing Ca2+ from the same internal store as that permeabilized by vasopressin, probably the endoplasmic reticulum, and potentiating the influx of extracellular Ca2+ caused by this hormone.

Cyclic AMP-evoked oscillations of intracellular [Ca2+] in guinea-pig hepatocytes

“…on a longer time scale, it must be noted that the Ca2+ signal decreases and disappears, reflecting the emptying of the Ca2+ stores. Also, experimental evidence indicates that the isoprenaline-evoked Controversies about a possible cAMP-mediated InsP3 synthesis in liver cells have been reported [6,[19][20][21][22]. To test this possibility, we used heparin, which inhibits both InsP3 binding and the resulting InsPJ-induced Ca2' release [8,9].…”

“…Also, recent work has shown that oscillations can be triggered directly by Ca2+ [4] or by bile acids in the absence of InsP3 [5]. We ISO 5piM have shown previously that glucagon, isoprenaline and dibutyryl cAMP increase [Ca2+]1 in rat liver cells, probably by releasing Ca2+ from the same internal store as that permeabilized by vasopressin [6,7]. In …”

Calcium: its modulation in liver by cross-talk between the actions of glucagon and calcium-mobilizing agonists

“…Combettes et al (1986) Combettes et al (1986) concluded that glucagon accelerates the fast phase of vasopressin-induced inflow and elevates the final internal store as that affected by vasopressin, and (b) potentiating the inflow of external Ca2+ induced by vasopressin. In a related study, Mauger and Claret (1986) showed that glucagon mobilizes Ca2+ from a pool that is also sensitive to the action of Ca2+-mobilizing agonists.…”

Effects of glucagon and vasopressin on hepatic Ca2+ release.

“…Glucagon released 107 + 57 nmol of Ca2+ per g of liver. Thus, the amount of Ca2+ released by glucagon was about 20-25% less than the Ca2+ released by equimolar amounts of vaso- (21) and recently with the combination of glucagon and vasopressin in isolated hepatocytes (22).…”