Adenosine receptors (AR) play an important role in the regulation processes for body temperature and vigilance states. During our previous studies, we noticed that aminophylline (a non-selective, blood-brain-barrier penetrably AR antagonist) could attenuate the effects of YZG-330 [(2R,3S,4R,5R)-2-(hydroxymethyl-5-(6-(((R)-1-phenylpropyl)amino)-9H-purin-9-yl)tetrahydrofuran-3, 4-diol] on lowering the body temperature. Hereby, we focused ourselves on the character of thermal regulation effect of YZG-330 in mice and tried to specify the receptor subtype via giving typical adenosine receptor antagonists. The results showed that both of the magnitude and lasting time of the effect that YZG-330 played on decreasing body temperature are in a dose-dependent manner: within the next 3 hour after intragastric administration (ig) of 0.25, 1 or 4 mg . kg-1 YZG-330, the extreme values on body temperature decreasing were (1.2 ± 0.3) °C, (3.6 ± 0.4) °C (P<0.001) and (7.4±0.5) °C (P<0.001), separately; whereas the duration that body temperature below 34 °C were 0, (10±5) and (153±4) min, separately. Adenosine A1 receptor (A1R) antagonist (DPCPX) could effectively reverse YZG-330's effect on decreasing body temperature, with intraperitoneal administration of DPCPX (5 mg . kg-1) 20 min prior than YZG-330 (4 mg.kg-1, ig), the extreme value on body temperature decreasing was (3.5 ± 0.7) °C (P<0.001), the duration that body temperature below 34 °C was (8±6) min (P<0.001). However, adenosine A2a receptor antagonist, SCH-58261, did not show any influence on the effects of YZG-330 at all. Combined with the fact that 8-SPT (a non-selective, blood-brain-barrier impenetrably AR antagonist) did not reverse the effect of YZG-330, we come to the conclusion that central-adenosine A, receptor plays a significant role on the thermal regulation effect of YZG-330.
Adenosine ; analogs & derivatives ; pharmacology ; Adenosine A1 Receptor Antagonists ; pharmacology ; Animals ; Body Temperature Regulation ; drug effects ; Mice ; Pyrimidines ; pharmacology ; Receptor, Adenosine A1 ; physiology ; Triazoles ; pharmacology ; Xanthines ; pharmacology

OBJECTIVETo compare the intervention effects of four traditional Chinese medicines (TCMs) with typical cold or hot property on body temperature and temperature-sensitive transient receptor potential ion channel proteins (TRPs) of rats with yeast-induced fever.

METHODThe pyrexia model was induced by injecting yeast suspension subcutaneously. Totally 108 male SD rats were randomly divided into the normal group, the model group, the Rhei Radix et Rhizoma treated group, the Coptidis Rhizoma treated group, the Euodiae Fructus treated group, and the Alpiniae Officinarum Rhizoma treated group, with 18 rats in each group. At the 4 h, 8 h and 12 h after injection of yeast, the rats were sacrificed to collect their hypothalamus and dorsal root ganglion. The expressions of TRPV1 and TRPM8 were detected by immunohistochemistry and Western blot method.

RESULTCompared with the normal group, after injection of yeast, the temperature of rats in the model group notably increased, and reached the peak at 8 h (P < 0.01). The TRPV1 level in hypothalamus and dorsal root ganglia (DRG) of the model group significantly increased, whereas the TRPM8 level significantly reduced. Compared with the model group, the Rhei Radix et Rhizoma group and the Coptidis Rhizoma group showed significant decrease in the high body temperature of rats caused by yeast, down-regulation in the expression of TRPV1, and up-regulation in the expression of TRPM8 (P < 0.05 or P < 0.01). Euodiae Fructus and Alpiniae Officinarum Rhizoma had no significant effect on either temperature or TRPs of fever rats.

CONCLUSIONRhei Radix et Rhizoma and Coptidis Rhizoma, both are TCMs with cold property, can reduce the temperature of fever rats induced by yeast, which may be related to their effective regulation of TRPV1 and TRPM8 in hypothalamus and DRG, while Euodiae Fructus and Alpiniae Officinarum Rhizoma had no relevant effect.

Animals ; Antipyretics ; administration & dosage ; chemistry ; Body Temperature Regulation ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Fever ; drug therapy ; immunology ; microbiology ; physiopathology ; Gene Expression Regulation ; drug effects ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Saccharomyces cerevisiae ; immunology ; TRPM Cation Channels ; genetics ; immunology ; TRPV Cation Channels ; genetics ; immunology

OBJECTIVETo study the influence of Radix aconiti lateralis preparata and Rhizoma zingiberis, two species of Chinese medicinal herbs with hot property, on energy metabolism and gene expression spectrum, and to analyze the possible mechanism of their effects.

METHODSForty-eight specific pathogen free Wistar rats were randomly divided into a Radix aconiti lateralis preparata group, a Rhizoma zingiberis group, and a control group. They were intragastrically treated with concentrated decoction of Radix aconiti lateralis preparata, Rhizoma zingiberis and normal saline respectively for 20 days. Toe temperature (TT), energy intake (EI), digestible energy (DE), and metabolizable energy (ME) were measured. The content of adenosine triphosphate (ATP) and energy charge (EC) in hepatic tissue were measured with high performance liquid chromatography (HPLC). The activity of ATPase and succinate dehydrogenase (SDH) in the liver were detected with chemical colorimetry. The gene expression in the liver was detected with Illumina's rat Ref-12 gene array. The differential expression genes were selected, annotated and classified based on Gene Ontology (GO). Real-time quantitative reverse-transcriptase PCR (Q-RT-PCR) was used to test the accuracy of results.

RESULTSCompared with the control group, the TT on the 10(th) day after the beginning of administration and ATP in the Radix aconiti lateralis preparata and Rhizoma zingiberis groups increased significantly (P<0.05). EI/body mass (BM), DE/BM, ME/BM, the hepatic EC and the activity of Na(+)-K(+)-ATPase, Ca(2+)-Mg(2+)-ATPase and SDH of liver increased significantly only in the Radix aconiti lateralis preparata group (P<0.05). There were 592 differential expression genes in the Radix aconiti lateralis preparata group and 1 159 in the Rhizoma zingiberis group compared with the control group. Among the differential expression genes, genes related to metabolic processes were the most significant based on GO analysis. There were 337 strips of gene differential expression in common in both Radix aconiti lateralis preparata and Rhizoma zingiberis groups compared with the control group.

CONCLUSIONSHerbs with hot property such as Radix aconiti lateralis preparata and Rhizoma zingiberis could improve the energy metabolism in rats, through influencing the metabolic process of sugar, lipid, and amino acid. It could also promote the production, storage, and utilization of energy by regulating the gene expression related to metabolism, which may be the main molecular mechanism of warming yang and dispelling cold for the treatment of the cold syndrome according to Chinese medicine theory.

Aconitum ; chemistry ; Adenosine Triphosphatases ; metabolism ; Adenosine Triphosphate ; metabolism ; Animals ; Body Temperature ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Energy Intake ; drug effects ; genetics ; Energy Metabolism ; drug effects ; genetics ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; drug effects ; Liver ; drug effects ; metabolism ; Male ; Rats ; Rats, Wistar ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; Rhizome ; chemistry ; Succinate Dehydrogenase ; metabolism

The theory of herbal properties of traditional Chinese medicine (TCM) is an indispensable part of theoretical system of TCM and plays an important role in the clinical prescription and application of TCM. In this theoretical system, the theory of four herbal properties takes a core and dominant position and becomes an indispensable part of TCM natures and actions. In combination of studies and experience, this essay proposes the latest discovery in modern biology-modern scientific connotation of cold and hot herbal properties on the basis of cold and hot perceptions of organism on the basis of analysis and summary of TRP channel protein and correlation of cold and hot perceptions of organism and thermoregulation, which is an effective approach to make breakthroughs in studies on modernization drive of the theory of four herbal properties of TCM.
Animals ; Body Temperature Regulation ; drug effects ; Drug Therapy ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Perception ; drug effects ; Transient Receptor Potential Channels ; genetics ; metabolism

PURPOSE: Anesthesia and surgery commonly cause hypothermia, and this caused by a combination of anesthetic-induced impairment of thermoregulatory control, a cold operation room environment and other factors that promote heat loss. All the general anesthetics markedly impair normal autonomic thermoregulatory control. The aim of this study is to evaluate the effect of two different types of propofol versus inhalation anesthetic on the body temperature. MATERIALS AND METHODS: In this randomized controlled study, 36 patients scheduled for elective laparoscopic gastrectomy were allocated into three groups; group S (sevoflurane, n=12), group L (lipid-emulsion propofol, n=12) and group M (micro-emulsion propofol, n=12). Anesthesia was maintained with typical doses of the study drugs and all the groups received continuous remifentanil infusion. The body temperature was continuously monitored after the induction of general anesthesia until the end of surgery. RESULTS: The body temperature was decreased in all the groups. The temperature gradient of each group (group S, group L and group M) at 180 minutes from induction of anesthesia was 2.5+/-0.6degrees C, 1.6+/-0.5degrees C and 2.3+/-0.6degrees C, respectively. The body temperature of group L was significantly higher than that of group S and group M at 30 minutes and 75 minute after induction of anesthesia, respectively. There were no temperature differences between group S and group M. CONCLUSION: The body temperature is maintained at a higher level in elderly patients anesthetized with lipid-emulsion propofol.
Aged ; Aging ; Anesthesia, General/*methods ; Anesthetics, Combined/administration & dosage ; Anesthetics, Inhalation/*administration & dosage ; Anesthetics, Intravenous/*administration & dosage ; Body Temperature/*drug effects ; Body Temperature Regulation/drug effects ; Fat Emulsions, Intravenous ; Female ; Humans ; Male ; Methyl Ethers/*administration & dosage ; Middle Aged ; Propofol/*administration & dosage

OBJECTIVETo investigate the role of oxotremorine in arginine vasopressin (AVP)-induced hypothermia and its effects on the behavioral thermoregulatory response.

METHODSCore temperature (Tc), brown adipose tissue (BAT) temperature and motor activities were monitored in undisturbed female SD rats using radiotelemetry. The behavioral thermoregulatory response was monitored in rats using radiotelemetric temperature gradient apparatus. Effect of AVP (10 microg/kg) and oxotremorine (0.25 mg/kg) on Tc, motor activities, BAT temperature (T(BAT)), grooming activities and the behavioral thermoregulatory response were observed in rats.

RESULTSAdministration of AVP and oxotremorine caused a significant drop in Tc, T(BAT), and an increases in grooming activities, respectively. The hypothermic responses were accompanied with a preference for cooler ambient temperature. Oxotremorine augmented the reduction of Tc, T(BAT), and the elevation of grooming activities resulting from AVP, and lasting a longer time. Administration of oxotremorine followed immediately by AVP injection in rats was also shown to induce a preference for cooler ambient temperature, but there was no significant difference compared with AVP.

CONCLUSIONAVP-induced hypothermia was related with the set point temperature reduction, inhibiton of BAT thermogenesis and an increases in grooming activities. Oxotremorine could participate in peripheral AVP-induced hypothermia by affecting BAT thermogenesis and behavioral thermoregulation.

Adipose Tissue, Brown ; drug effects ; physiology ; Animals ; Arginine Vasopressin ; pharmacology ; Behavior, Animal ; Body Temperature Regulation ; Female ; Hypothermia, Induced ; Oxotremorine ; pharmacology ; Rats ; Rats, Sprague-Dawley

AIMTo determine whether bombesin prevents IFN-alpha-induced fever and it's possible mechanism.

METHODSEffects of BN on changes in body temperature and arginine vasopressin(AVP) content in the ventral septal area(VSA) and hypothalamus were measured in the rats following intracerebroventricular (ICV) injection of IFN-alpha.

RESULTS(1) IFN-alpha produced a dose-dependent rise in colonic temperature simultaneously with increase in AVP content in the VSA in the rats. (2) BN produced a dose-dependent hypothermia and significantly elevated AVP content in the VSA in rats. (3) BN injected intracerebroventricularly at 30 min after IFN-alpha prevented the increase in colonic temperature which recovered to the control level as well as AVP content in the VSA in rats at 150 min.

CONCLUSIONAVP in the VSA may play a role in IFN-alpha-induced fever. AVP in the VSA may play a partial role in the BN antipyretic action and hypothermic action.

Animals ; Arginine Vasopressin ; metabolism ; Body Temperature Regulation ; drug effects ; Bombesin ; pharmacology ; Brain ; drug effects ; metabolism ; Fever ; chemically induced ; physiopathology ; Interferon-alpha ; adverse effects ; Male ; Rats ; Rats, Wistar

AIMTo explore the role of nitric oxide (NO) in arginine vasopressin (AVP)-induced hypothermia.

METHODSColonic temperature was measured at 30 min intervals with a digital thermometer. Effects of central and peripheral administration of nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) on AVP-induced hypothermia were observed in rats.

RESULTS(1) Intravenous injection (i.v.) of AVP (4 microg x kg(-1)) and L-NAME (30 mg x kg(-1)) produced a significant drop in body temperature, respectively. Coadministration of L-NAME i.v. with AVP i.v. did not significantly influence the magnitude of AVP-induced hypothermia. (2) Intracerebroventricular (i.c.v.) injection of L-NAME (1 mg x kg(-1)) caused a significant increase in body temperature, but when the treatments with AVP and L-NAME were combined, i.c.v. injection of L-NAME markedly blocked the hypothermic effect of AVP intravenous injection.

CONCLUSIONEndogenous NO in the central nervous system plays a major role in AVP-induced hypothermia. In addition, central NO seems to play a tonic thermoregulatory role by reducing normal body temperature because an increase in body temperature was observed after treatment with NOS inhibitor L-NAME.

Animals ; Arginine Vasopressin ; pharmacology ; Body Temperature ; drug effects ; Body Temperature Regulation ; drug effects ; Enzyme Inhibitors ; pharmacology ; Hypothermia ; chemically induced ; Male ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; antagonists & inhibitors ; Rats ; Rats, Wistar

Animals ; Arcuate Nucleus of Hypothalamus ; drug effects ; metabolism ; Body Temperature Regulation ; Cyclic AMP ; metabolism ; Dinoprostone ; metabolism ; Eugenol ; pharmacology ; Fever ; metabolism ; Preoptic Area ; drug effects ; metabolism ; Rabbits

BACKGROUND: Body temperature is usually regulated by opposing controls of heat production and heat loss. However, systemic administration of capsaicin, the pungent ingredient of hot peppers, facilitated heat production and heat loss simultaneously in rats. We recently found that the capsaicin-induced heat loss and heat production occur simultaneously and that the biphasic change in body temperature is a sum of transient heat loss and long-lasting heat production. Moreover, suppression of the heat loss response did not affect capsaicin-induced heat production and suppression of heat production did not affect capsaicin-induced heat loss. These observations suggest the independent peripheral mechanisms of capsaicin-induced thermal responses. Thus, the capsaicin-induced thermal responses apparently lack an integrated control. METHODS: Male Wistar rats were maintained at an ambient temperature of 24 1 degrees C on a 12 h on-off lighting schedule at least for two weeks before the experiments. They were anesthetized with urethane (1.5 g/kg, i.p.) and placed on a heating pad, which was kept between 29 and 30 degrees C. Skin temperature(Ts) was measured with a small thermistor, which was taped to the dorsal surface of the rat's tail, to assess vasoactive changes indirectly. Colonic temperature(Tc) was measured with another thermistor inserted about 60 mm into the anus. O2 consumption was measured by the open-circuit method, and values were corrected for metabolic body size (kg0.75). Capsaicin (Sigma) was dissolved in a solution comprising 80+ACU- saline, 10+ACU- Tween 80, and 10+ACU- ethanol, and injected subcutaneously at a dose of 5 mg/kg. Each rat received a single injection of capsaicin because repeated administration of capsaicin renders an animal insensitive to the subsequent administration of capsaicin. Laminectomy was performed at the level of the first and second cervical vertebrae to expose the cervical spinal cord for sectioning. The brain was transected at 4-mm rostral from the interaural line with an L-shaped knife. RESULTS: After administration of capsaicin, O2 consumption increased from 13.5 0.4 mL/min/kg0.75 at 0 min to a peak of 15.9 0.4 mL/min/kg0.75 at 71 min and gradually declined but remained higher than the basal value until the end of the 4-h observation period. Ts also immediately increased from 27.7 0.2 degrees C to 31.9 0.3 degrees C at 39 min, and it returned to the baseline level within 90 min after the capsaicin administration. Tc initially decreased from 37.1 0.1 degrees C to 36.8 0.2 degrees C at 43 min and then gradually increased over the baseline level and remained at 37.6 0.2 degrees C until the end of the experiment. In spinalized rats, the capsaicin-induced increases in O2 consumption was largely attenuated, while the basal O2 consumption was similar to that of control rats. The basal Ts of spinalized rats was 32.4 0.3 degrees C, which was higher than that of control rats. Capsaicin increased Ts by less than 1 degree C, and Tc did not change after the capsaicin administration. O2 consumption of decerebrated rats was statistically higher than that of control rats after the injection of capsaicin. However, capsaicin did not increase Ts, showing a lack of a vasodilatory response. Decerebration between the hypothalamus and midbrain prevented the capsaicin-induced heat loss but not the heat production response. CONCLUSION: These results show that the capsaicin-induced heat production and heat loss are controlled separately by the brainstem and by the forebrain, respectively, and suggest that the body temperature regulation is performed without an integrative center.
Animal ; Body Temperature Regulation/drug effects+ACo- ; Brain/physiology ; Brain/drug effects ; Capsaicin/pharmacology+ACo- ; Decerebrate State ; Male ; Oxygen Consumption/drug effects ; Rats ; Rats, Wistar