cAMP and Ca2+Involvement in the Mitochondrial Response of Cultured Fetal Rat Hepatocytes to Adrenaline (original) (raw)

1997, Experimental Cell Research

The transition from fetus to neonate involves a activity of mitochondria from fetal hepatocytes in primary culture was studied. In the absence of adrena-shift from a relatively anaerobic environment to an line, the respiratory control ratio (RCR) of mitochon-aerobic one. This situation requires the rapid postnadria increased during the first 3 days of culture due to tal acquisition of efficient energy-transducing mitoa decrease in the rate of state 4 respiration. The preschondria. In fact, liver mitochondria reach adult ence of adrenaline in the incubation medium further functional capacity within the first hour of extrauterincreased the mitochondrial RCR through a decrease ine life, as shown by the sharp increase in the respirain the rate of respiration in state 4 and to an increase tory control ratio (RCR) 2 [1] and in the activities of in the respiration rate in state 3. The effect of adrenathe respiratory-chain and of ATP-synthase comline was mimicked by dibutyryl-cAMP, forskolin, and plexes observed during this short period [2]. Postnaisobutyl methyl xanthine. All these compounds intal mitochondrial differentiation is brought about by creased cAMP concentrations, suggesting that cAMP the synergistic action of two main processes, i.e., an may be involved in the effect of adrenaline. The inenhancement of the synthesis of proteins involved crease in intracellular free Ca 2/ concentrations caused in energy transduction [2] and an accumulation of by phenylephrine, vasopressin, or thapsigargin was adenine nucleotides in the mitochondrial matrix [1, also accompanied by an increase in the RCR, sug-3], which occurs shortly after birth [1, 3-5]. gesting that both phenomena are associated. Dibu-It has been suggested that the hormone status of tyryl-cAMP also increased free Ca 2/ concentrations, the newborn probably modulates the rate of adenine suggesting that the effects of cAMP may be mediated nucleotide accumulation either directly or indirectly by free Ca 2/ concentrations. Adrenaline, dibutyrylthrough changes in the cytoplasmic ATP/ADP ratio [3, cAMP, phenylephrine, vasopressin, and thapsigargin 6, 7]. Thus, immediately after birth a sharp increase promoted adenine nucleotide accumulation in mitoin plasma catecholamine concentrations occurs [8-10] chondria; this may be an intermediate step in the actiwhich has been proposed to be responsible for resisvation of mitochondrial respiratory function. These results suggest that the stimulatory effect of adrena-tance to postnatal hypoxia in newborns [9]. It should line on mitochondrial maturation in cultured fetal rat be mentioned that hypoxia may cause a decrease in hepatocytes may be exerted through a mechanism in mitochondrial adenine nucleotide concentrations while which both cAMP and Ca 2/ act as second messengers. exposure to adrenaline would enhance total adenine It is concluded that the effect of adrenaline on mitonucleotide contents in vitro [see 11]. chondrial maturation is exerted by both a-and b-adb-Adrenergic receptor functions are predominant in renergic mechanisms and is mediated by the increase fetal rat liver but their coupling to adenylate cyclase in adenine nucleotide contents of mitochondria. ᭧ 1997 decreases during early neonatal life [12], a-adrenergic Academic Press functions being predominant [see 13] after maturation.