cAMP and CaInvolvement in the Mitochondrial Response of Cultured Fetal Rat Hepatocytes to Adrenaline

The effect of adrenaline on the control of respiratory activity of mitochondria from fetal hepatocytes in primary culture was studied. In the absence of adrenaline, the respiratory control ratio (RCR) of mitochondria increased during the first 3 days of culture due to a decrease in the rate of state 4 respiration. The presence of adrenaline in the incubation medium further increased the mitochondrial RCR through a decrease in the rate of respiration in state 4 and to an increase in the respiration rate in state 3. The effect of adrenaline was mimicked by dibutyryl-cAMP, forskolin, and isobutyl methyl xanthine. All these compounds increased cAMP concentrations, suggesting that cAMP may be involved in the effect of adrenaline. The increase in intracellular free Ca²⁺concentrations caused by phenylephrine, vasopressin, or thapsigargin was also accompanied by an increase in the RCR, suggesting that both phenomena are associated. Dibutyryl-cAMP also increased free Ca²⁺concentrations, suggesting that the effects of cAMP may be mediated by free Ca²⁺concentrations. Adrenaline, dibutyryl-cAMP, phenylephrine, vasopressin, and thapsigargin promoted adenine nucleotide accumulation in mitochondria; this may be an intermediate step in the activation of mitochondrial respiratory function. These results suggest that the stimulatory effect of adrenaline on mitochondrial maturation in cultured fetal rat hepatocytes may be exerted through a mechanism in which both cAMP and Ca²⁺act as second messengers. It is concluded that the effect of adrenaline on mitochondrial maturation is exerted by both α- and β-adrenergic mechanisms and is mediated by the increase in adenine nucleotide contents of mitochondria.     

Increase of Formation of Methylamine and Formaldehyde In Vivo after Administration of Nicotine and the Potential Cytotoxicity

Methylamine is a constituent of cigarette smoke and the major end product of nicotine metabolism. Smoking or nicotine can induce the release of adrenaline, which is in turn deaminated by monoamine oxidase, also producing methylamine. We found that the urinary level of methylamine was significantly elevated following administration of nicotine (25 mg/Kg, i.p.). Semicarbazide-sensitive amine oxidase (SSAO) inhibitors further increased the excretion of methylamine induced by nicotine. Following administration of L-(—)-[N-methyl-³H]nicotine long-lasting irreversible radioactive adducts were detected in different mouse tissues and such adduct formation could be blocked by selective SSAO inhibitors. These adducts are probably cross-linked oligoprotein complexes cross-linked by formaldehyde. The findings support the idea that nicotine can enhance SSAO/methylamine-mediated increase of formaldehyde and oxidative stress and this could in part contribute the adverse effect of health associated with smoking.     

延髓头端腹外侧区肾上腺素能机制在应激性升压反应和心动过速中的作用

目的和方法：在延髓头端腹外侧区（ｒＶＬＭ）内注射肾上腺素（Ｅ）旨在能否影响正常大鼠的血压和心率,并分析ｒＶＬＭ内肾上腺素能机制在应激性升压反应和心动过速中的作用。将清醒ＳＤ大鼠四肢固定在铁丝网架上,经束缚方法观察应激性血压和心率的变化。结果：①束缚清醒大鼠可引起升压反应和心动过速;②在双侧ｒＶＬＭ内注射微量Ｅ可引起血压和心率垢明显增加,此作用可被在同一区域双侧注射α－肾上腺素能受体阻断剂（酚妥拉明     

The effect of adrenaline and Walker‐256 tumour‐induced cachexia upon Kupffer cell metabolism

Kupffer cells (KC), the liver macrophages, are able to produce PGE₂, which is involved in immune suppression and in the aggravation of cancer cachexia due to interference with lipid metabolism in the liver. Since tumour‐bearing (TB) rats present high plasma epinephrine levels, and this hormone is able to affect macrophage metabolism and function, we have assessed the effect of epinephrine (5 nm ) upon Kupffer cell PGE₂ production. Epinephrine induced increased production of PGE₂ both by control (3·5‐fold) and TB rats (27 per cent) KC, an effect blocked by propranolol. Enhancement of cAMP content in the cells by addition of isoproterenol (0·1 μm ) to the incubations, however, failed to induce the same response in the cells. Nevertheless, when phenylephrine (1 μm ) was added to the incubation, a similar pattern of PGE₂ production to that observed for epinephrine was found for control and TB rat KC. We propose that the effect of epinephrine upon KC PGE₂ production is mediated by α‐adrenergic receptors and that Ca²⁺ is involved in the response, since increasing concentrations of the ion added to the incubation medium (0·25, 0·5 and 1·0 mm ) enhanced the eicosanoid production, while EDTA abolished the response. Copyright © 1999 John Wiley & Sons, Ltd.     

Effect of adrenaline on lymphocyte metabolism and function. A mechanism involving cAMP and hydrogen peroxide

This study examined the effect of adrenaline on lymphocyte metabolism and function. The following parameters were addressed: cell proliferation, glucose and glutamine metabolism as indicated by the measurement of enzyme activities, the utilization of metabolites and production and oxidation of substrates. We also evaluated the involvement of beta-receptors in this response as well as the possible effect of cAMP and hydrogen peroxide in the process of lymphocyte activation by adrenaline. The results indicated that adrenaline is able to induce metabolic changes in lymphocytes that are related to enhanced proliferative capacity, but under physiological conditions fails to initiate the process, the catecholamine could, increase cell proliferation via increased production of H₂O₂ by macrophages, since this reactive oxygen intermediate can act as a trigger for lymphocyte activation. The results also showed that distinct populations of lymphocytes present different responses to adrenaline activation, as demonstrated by cells obtained from the same site but exposed to different mitogens such as LPS and ConA. © 1997 John Wiley & Sons, Ltd.     

Effect of urate on the lactoperoxidase catalyzed oxidation of adrenaline

Lactoperoxidase is an iron containing enzyme, which is an essential component of the defense system of mammalian secretary fluids. The enzyme readily oxidizes adrenaline and other catecholamines to coloured aminochrome products. A K_m-value of 1.21 mM and a catalytic constant (k = V_\max/[Enz]) of 15.5 × 10³ min^–1 characterized the reaction between lactoperoxidase and adrenaline at pH 7.4. Urate was found to activate the enzyme catalyzed oxidation of adrenaline in a competitive manner, the effect decreasing with increasing adrenaline concentration. Lactoperoxidase was able to catalyze the oxidation of urate. However, urate was a much poorer substrate than adrenaline, and it seems unlikely that urate activates by functioning as a free, redox cycling intermediate between enzyme and adrenaline. The activation mechanism probably involves an urate-lactoperoxidase complex.     

Increase in Swimming Endurance Capacity of Mice by Capsaicin-induced Adrenal Catecholamine Secretion

Increase in endurance swimming capacity caused by capsaicin (CAP), a pungent component of red pepper, -induced increase of fat metabolism in mice was investigated using an adjustable-current water pool. The mice administered CAP via a stomach tube, showed longer swimming time until exhaustion than the control group of mice, in a dose-dependent manner. The maximal effect was observed at a dose of 10 mg/kg while more than 15 mg/kg had no effect. The increase of endurance was observed only when CAP was administered two hours before swimming. After the administration of CAP, the serum glucose concentration rapidly increased and then decreased within 60min, while the concentration of serum-free fatty acids gradually increased through 3 hours. The residual glycogen concentration of the gastrocnemius muscle after 30 min of swimming was significantly higher in the CAP-administered mice than in control mice, suggesting that use of the serum free fatty acids spared muscle glycogen consumption. The serum adrenaline concentration significantly increased with twin peaks at 30 min and two hours after administration of CAP. An experiment using adrenalectomized mice was done to confirm that the effect of CAP is due to increased energy metabolism through the secretion of adrenaline from the adrenal gland. The swimming endurance capacity of the adrenalectomized mice was not increased by CAP administration, although adrenaline injection induced a 58% increase in the endurance time. These results suggest that the increase of swimming endurance induced by CAP in mice is caused by an increase in fatty acid utilization due to CAP-induced adrenal catecholamine secretion.     

TRPA1 Agonists—Allyl Isothiocyanate and Cinnamaldehyde—Induce Adrenaline Secretion

Thermosensitive transient receptor potential (TRP) channels, especially TRPV1 and TRPA1, are activated by the pungent compounds present in spices. TRPV1 activation by the intake of capsaicin, the irritant in hot pepper, induces adrenaline secretion and increases energy consumption. TRPV1 is mainly expressed in the sensory neurons and coexpressed with TRPA1 at a high frequency. However, the mechanism underlying adrenaline secretion by TRPA1 agonists such as allyl isothiocyanate (AITC) and cinnamaldehyde (CNA), the pungent ingredients in mustard and cinnamon, is not known. We examined whether AITC and CNA could induce adrenaline secretion in anesthetized rats. An intravenous injection of AITC or CNA (10 mg/kg) increased adrenaline secretion. These responses disappeared completely in capsaicin-treated rats with an impaired sensory nerve function. Moreover, pretreatment with cholinergic blockers (hexamethonium and atropine) attenuated the AITC- or CNA-induced adrenaline secretion. These results suggest that TRPA1 agonists activate the sensory nerves and induce adrenaline secretion via the central nervous system.     

Capsaicinol: Synthesis by Allylic Oxidation and Its Effect on TRPV1-Expressing Cells and Adrenaline Secretion in Rats

Capsaicinol is an ingredient of hot red pepper. In this study, we developed a novel method for capsaicinol synthesis and examined capsaicinol’s physiological effects on capsaicin receptor (TRPV1)-related actions. Allylic oxidation of capsaicin by palladium acetate (Pd(OAc)₂) resulted in the formation of (±)-capsaicinol acetate at a 7.2% yield in a single step. The effectiveness of (±)-capsaicinol in TRPV1 activation (EC₅₀=1.1 μM) was found to be weaker than that of capsaicin (EC₅₀=0.017 μM), whereas the efficacy of (±)-capsaicinol reached 75% of that of capsaicin. Intravenous administration of (±)-capsaicinol in anesthetized rats dose-dependently enhanced adrenaline secretion from the adrenal gland. The response to a 5 mg/kg-dose of (±)-capsaicinol was comparable to that of a 0.05 mg/kg-dose of capsaicin. The relative pungency of capsaicinol to capsaicin was coincident with the relative effectiveness in inducing these TRPV1-related actions.     

Induction and Promotion of Flowering by Heat-Treated Catecholamines in Lemna paucicostata

Alkali- and heat-treated norepinephrine, a catecholamine, induced flowering of short-day (SD) plant Lemna paucicostata 151 even under long-day (LD) conditions. Flowering induced with a lower concentration of heat-treated norepinephrine was promoted under SD conditions but inhibited by a night break. The related compounds L-dopa and dopamine also promoted flowering under SD conditions when they were heat-treated.