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R C Haynes

Publications and source records attributed to R C Haynes.

At least 37 records · Page 2Linked to original sources
PubMed1980

The control of uncoupler-activated ATPase activity in rat liver mitochondria by adenine nucleotide transport. The effect of glucagon treatment.

Acute treatment of rats with glucagon increased the Vmax but did not change the Km (ATP) of uncoupler-activated ATPase in subsequently isolated hepatic mitochondria. The hormonal stimulation was evident in mitoplasts but not in submitochondrial particles nor after lysis of the mitochondria. The rate of Pi-ATP exchange of intact mitochondria was also increased by glucagon treatment. The hormonal stimulation of ATPase was dependent on concentration of the uncouplers, being absent at minimally effective concentrations while high concentrations inhibited the ATPase. Inhibitors of adenine nucleotide transport decreased ATPase activity without evidence of sigmoidicity in the response curves and produced linear Dixon plots indicating that the ATPase was limited by the rate of adenine nucleotide transport. Glucagon treatment did not change the number of binding sites for transport inhibitors. Glucagon stimulated the rate of transport of ATP as measured by accumulation of labeled nucleotide. This was found to be the consequence of an enlarged pool of exchangeable adenine nucleotides within mitochondria from glucagon-treated animals. This increase in mitochondrial nucleotides appears to explain a number of the effects of hormones on mitochondrial functions including the stimulation of uncoupler-activated ATPase activity.

Adenosine Triphosphatases↗
PubMed1978

Glucagon treatment stimulates the metabolism of hepatic submitochondrial particles.

Hepatic submitochondrial particles, prepared at neutral pH from rats pretreated with glucagon, exhibited stimulated rates of State 3 and uncoupled respiration when succinate or NADH were the substrates, but not when ascorbate plus N,N,N',N'-tetramethyl-p-phenylenediamine were employed. Measurements of 8-anilino-1-naphthalenesulfonic acid fluorescence in the particles indicated that glucagon treatment resulted in a stimulation of energization supported by succinate respiration or ATP hydrolysis. Similarly, the energy-linked pyridine nucleotide transhydrogenase and reverse electron flow reactions driven by succinate oxidation or ATP were also stimulated. The results indicate that mitochondrial substrate transport is not the prime locus of glucagon action. It is suggested that the increased level of energization in particles prepared from glucagon-treated rats is a reflection of a stimulation of the respiratory chain, possibly between cytochromes b and c, and the ATP-forming reactions.

Adenosine Triphosphate↗
PubMed1975

The hormonal control of gluconeogenesis by regulation of mitochondrial pyruvate carboxylation in isolated rat liver cells.

The possibility that hormones control hepatic gluconeogenesis via the regulation of the rate of mitochondrial pyruvate carboxylation was investigated with the use of suspensions of liver cells isolated from fasted rats. The mitochondria prepared from liver cells were judged in good condition as they exhibited satisfactory phosphorus-oxygen and respiratory control ratios and transported Ca2+ and K+ ions in an energy-dependent manner. Addition of glucagon, epinephrine, or cyclic adenosine 3':5'-monophosphate to liver cells caused a 50 to 80% increase in the rate of glucose synthesis from lactate. When mitochondria were isolated from the cells after treatment with these agonists, they displayed 2- to 3-fold increases in the rate of pyruvate carboxylation, pyruvate decarboxylation, and pyruvate uptake. These mitochondrial changes are similar to those obtained in hepatic mitochondria prepared from intact, hormone-treated rats. The mitochondrial responses were specific for agents that stimulated gluconeogenesis; no response occurred with 5'-AMP or cyclic adenosine 2':3'-monophosphate. In the cell suspensions, the dose response curves for the activation of mitochondrial pyruvate metabolism and for increased glucose synthesis from L-lactate were coincident with four different agonists. The mitochondrial changes resulting from stimulation with glucagon developed in 1 to 2 min after the rise in cyclic adenosine 3':5'-monophosphate and occurred at least as early as the increase in the rate of gluconeogenesis. When the intracellular level of cyclic adenosine 3':5'-monophosphate returned to basal values, the rates of mitochondrial pyruvate carboxylation and glucose synthesis also declined to control levels. It is concluded that the rate of mitochondrial pyruvate metabolisms can be increased by hormones and cyclic nucleotides and that control of mitochondrial pyruvate carboxylation is an important regulatory site of hepatic gluconeogenesis.

Animals↗
PubMed1975

Effects of glucagon and other peptides on fixation of CO2 by rat liver mitochondria.

Glucagon and glucagon fragments from the carboxyl terminal end of the protein act at 0.01 to 0.1 mM concentrations on isolated rat liver mitochondria to sustain the rate of fixation of CO2 in the presence of pyruvate. The rate of decarboxylation of pyruvate is also increased by these substances. Similar effects are found with bacitracin, vanocomycin and cephalothin but not with any other of the proteins, peptides and antibiotics tested. The action of glucagon requires the presence of added magnesum ion. The addition of glucagon results in a better maintenance of adenosine triphosphate (ATP), and it leads to a greater degree of swelling of the mitochondria during the incubation. The effect of glucagon is partially mimicked by atractyloside, but it appears that glucagon is not exerting its effect by an atractyloside-like action. Added ATP obliterates the effect of added glucagon by sustaining fixation of CO2 However in incubations made in the presence of lower than usual levels of inorganic phosphate (2 mM vs. 8 mM) an effect of glucagon can be seen in the presence of ATP.

Adenosine Triphosphate↗
PubMed1974

Hormonal drugs.

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Anti-Inflammatory Agents↗