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T F Lee

Publications and source records attributed to T F Lee.

18 recordsLinked to original sources
PubMed1992

Decrease in cold tolerance of aged rats caused by the enhanced endogenous adenosine activity.

During severe cold exposure, old rats (24-28 months) were less capable of maintaining their body temperature compared to young rats (3-6 months) due to lower rate of heat production. Single injection of adenosine deaminase (AD) (converts adenosine to inosine) significantly increased thermogenesis in both young and old rats. However, doubling the dose of AD was required for optimal thermogenic response in old rats. In contrast, the similar enhancements in both thermogenesis and cold tolerance were observed in both young and old rats receiving the same optimal doses of specific adenosine receptor antagonists. These results lead to the suggestion that the lower capability of aged rats to withstand cold exposure could be due to an increase in adenosine stimulation because of the decreased endogenous AD activity rather than an increase in adenosine receptor sensitivity. This notion is further supported by the finding that the AD activity in the neck muscle, a key site for shivering thermogenesis, was significantly lower in old rats as compared to their younger counterparts before and after cold exposure.

Adenosine↗
PubMed1991

Seasonal changes in methionine-enkephalin immunoreactivity in the brain of a hibernator, Spermophilus columbianus.

To identify the actual location of central endogenous opioid systems which may be involved in regulating the hibernation cycle, differences in the pattern of central methionine-enkephalin (Met-EK) immunoreactivity were compared between hibernating (body temperature, Tb = 7 degrees C) and non-hibernating (Tb = 37 degrees C) Columbian ground squirrels using the peroxidase-antiperoxidase technique. In non-hibernating animals, Met-EK-immunoreactive perikarya were observed in telencephalic (putamen, caudate nucleus, medial septum-diagonal band complex, amygdala) and diencephalic (periventricular hypothalamic nucleus, lateral hypothalamic area) regions, whereas immunoreactive fibers were found in the lateral septum, stria terminalis nucleus, various hypothalamic areas, arcuate nucleus, median eminence, thalamic intralaminar, periventricular nucleus and lateral habenular nucleus. Compared to the non-hibernating animal, a marked increase in the number of Met-EK-immunoreactive fibers was found in the lateral septal nucleus, the periventricular nucleus, the intralaminar thalamus and the paraventricular hypothalamus of hibernating ground squirrels. Since these changes in immunoreactivity were not observed in the artificially induced hypothermic ground squirrels (Tb = 7 degrees C), it is unlikely that the dissimilarity in immunoreactivity between animals from different hibernating phases is due to differences in their Tb. In combination with our previous studies, these results tend to suggest that hibernation may be brought about by an increase in endogenous opioid activity, especially in the lateral septal region.

Animals↗
PubMed1991

State-dependent variation in the inhibitory effect of [D-Ala2, D-Leu5]-enkephalin on hippocampal serotonin release in ground squirrels.

Accumulated evidence has suggested that increased endogenous opioid activities may facilitate the onset of hibernation either directly or possibly through modulation of other neurotransmitter systems. The seasonal change of [D-Ala2, D-Leu5]-enkephalin (DADLE), a delta receptor agonist, in modulating K+ (35 mM)-induced [3H]-5-hydroxytryptamine (5-HT) release from the hippocampal and hypothalamic slices of euthermic and hibernating Richardsons' ground squirrels was therefore investigated. DADLE (0.1-10 microM) had no effect on 5-HT release in the hypothalamic slices but elicited a dose-related inhibition on [3H]-5-HT release from the hippocampal slices of the euthermic ground squirrel. The inhibitory effect of DADLE was completely reversed by naloxone (10 microM), but not by tetrodotoxin (1 microM). In contrast, DADLE failed to alter the K(+)-induced 5-HT release from the hippocampal slices of the hibernating ground squirrel. This state-dependent reduction in responsiveness to an opioid is consistent with the hypothesis that enhanced endogenous opioid activity in the hibernating phase could lead to down regulation of the opioid receptors and minimize its inhibition on hippocampal serotonergic activity. A high 5-HT activity would inhibit midbrain reticular activating system indirectly through non-serotonergic fibers, which in turn facilitate the onset or maintenance of hibernation.

Animals↗
PubMed1990

Improvement of cold tolerance by selective A1 adenosine receptor antagonists in rats.

Previously we have shown that the improvement of cold tolerance by theophylline is due to antagonism at adenosine receptors rather than inhibition of phosphodiesterase. Since theophylline is a nonselective adenosine receptor antagonist for both A1 and A2 receptors, the present study investigated the adenosine receptor subtype involved in theophylline's action. Acute systemic injection of selective A1 receptor antagonists (1,3-dialkyl-8-aryl or 1,3-dialkyl-8-cyclopentyl xanthine derivatives) significantly increased both the total and maximal heat production as well as cold tolerance. In contrast, injection of a relatively selective A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (compound No. 19), failed to significantly alter the thermogenic response of the rat under cold exposure. Further, the relative effectiveness of these compounds in increasing total thermogenesis was positively correlated with their potency in blocking the A1 adenosine receptor (r = .52, p less than 0.01), but not in A2 adenosine receptor (r = .20, p less than 0.2). It is likely that the thermally beneficial effects of adenosine A1 antagonists are due to their attenuation of the inhibitory effects of endogenously released adenosine on lipolysis and glucose utilization, resulting in increased substrate mobilization and utilization for enhanced thermogenesis.

Animals↗
PubMed1990

Do adenosine antagonists improve cold tolerance by reducing hypothalamic adenosine activity in rats?

Previously we have shown that systemic injection of adenosine antagonists can significantly improve cold tolerance in both rats and humans. However, it is not clear whether systemic administration of adenosine antagonist acts peripherally or centrally at the thermoregulatory site. To resolve this, theophylline (nonselective adenosine receptor blocker), cyclopentyltheophylline (selective A1 receptor blocker) or adenosine deaminase (an enzyme which inactivates adenosine by converting it into inosine) was injected directly into preoptic anterior hypothalamus (POAH) of rats and their thermogenic responses assessed. In contrast to that observed after systemic administration, intrahypothalamic injection of either adenosine antagonists or deaminase at various doses failed to elicit any enhancement in heat production beyond that of the controls. These results suggest that the beneficial effect of systemically injected adenosine antagonists in improving cold tolerance is not the result of altering the thermoregulatory functions mediated via the POAH.

Adenosine Deaminase↗
PubMed1990

Effect of intracerebroventricular injection of neokyotorphin on the thermoregulatory responses in rats.

Intracerebroventricular injection of neokyotorphin (NKT) (0.5-2.0 micrograms) caused a dose-related increase in body temperature (Tb) of rats maintained at 28 degrees C. The change in Tb of the rat induced by the optimal dose of NKT (1 microgram) was attenuated when the rat was exposed to 18 degrees C. At both ambient temperatures, heat production was not affected but heat loss was significantly reduced at 28 degrees C in rats receiving 1 microgram NKT. Pretreatment with naloxone (5 mg/kg, IP) significantly reduced the hyperthermic effect induced by NKT (1 microgram). These results suggest that NKT can affect the prevailing thermoregulatory heat loss activities and this effect may be mediated through stimulated release of endogenous opioids.

Amino Acid Sequence↗
PubMed1990

Enhancement of maximal thermogenesis by reducing endogenous adenosine activity in the rat.

Adenosine has been shown in vitro to be a potent antilipolytic agent and an inhibitor of insulin-stimulated glucose utilization in skeletal muscle. To test whether endogenously produced adenosine (e.g., from ATP hydrolysis) shares these deleterious effects on substrate mobilization and utilization and thus limits maximum thermogenesis in vivo, adenosine deaminase (converts adenosine to inosine) was given to rats 15 min before cold exposure. Significant (P less than 0.05) increases in thermogenesis were observed under both well-fed (100 units/kg ip) and food-rationed (200 units/kg ip) states. Significant (P less than 0.05) increases in thermogenesis and cold resistance were also observed after pretreatment with selective adenosine receptor antagonists [8-cyclopentyltheophylline (1 microgram/kg ip) greater than 1,3-dipropyl-8-p-sulfophenylxanthine (1.25 mg/kg ip) greater than aminophylline (18.7 mg/kg ip)], indicating an A1-receptor-mediated effect. These results indicate that endogenously released adenosine can indeed attenuate the thermogenic capacity in severe cold and that adenosine antagonists, especially those selective for A1-receptor, are useful in improving cold resistance under varying nutritional states.

Adenosine↗
PubMed1979

Effects of morphine and related drugs on core temperature of two strains of rat.

The changes in core temperature induced by low (5 mg/kg) and high (40 mg/kg) doses of morphine were compared in Wistar and Sprague-Dawley rats. In Sprague-Dawley rats the low dose caused a hyperthermia and the high dose a hypothermia but in Wistar rats both doses caused a hyperthermia. In either case the change in core temperature was antagonized by naloxone (2 mg/kg). Tolerance to the effects of the high dose of morphine developed in both strains of rat. Dextromoramide (3.75 and 15 mg/kg) also had an effect on core temperature, but in this case the responses of the strains were opposite to those seen with morphine. Laevomoramide was relatively ineffective. Naloxone (2 mg/kg) had no effect on the ability of rats of either strain to withstand heat or cold stress, providing no evidence that endogenous morphine-like substances have a physiological role in thermoregulation.

Animals↗
PubMed1979

Evidence for an endogenous dopamine-mediated hypothermia in the rat.

1 Unilateral intrahypothalamic injection of either dopamine (10 mug) or amphetamine (10 mug) caused a fall in core temperature in the rat. Pimozide (0.5 mg/kg, i.p.) significantly reduced the hypothermic response, whereas pretreatment with phentolamine (1 mg/kg, i.p.) or methysergide (5 mg/kg, i.p.) was ineffective.2 Systemic pretreatment with cocaine (20 mg/kg) abolished the hypothermic effect of amphetamine, but slightly enhanced the hypothermic response to dopamine.3 Systemic pretreatment with tranylcypromine (10 mg/kg) had no significant effect on the fall in core temperature induced by either amphetamine or dopamine.4 Intraperitoneal injection of cocaine and tranylcypromine, on their own, caused a fall in core temperature in the rat, which was significantly antagonized by either systemic or central pretreatment with pimozide. Phentolamine and methysergide failed to block the hypothermia.5 Unilateral intrahypothalamic injection of cocaine (20 mug) or tranylcypromine (10 mug) also caused a significant fall in core temperature, which was reduced by intrahypothalamic pretreatment with pimozide (0.5 mug), but not significantly changed by pretreatment with phentolamine (25 mug) or methysergide (5 mug).6 These results provide evidence for the presence of a dopaminergic system within the preoptic region, which mediates a lowering of core temperature in the rat.

Amphetamine↗
PubMed1978

Dopamine receptors in the central thermoregulatory pathways of the rat.

1. Intrahypothalamic injection of either dopamine (10 microgram) or apomorphine (10 microgram) in a dose volume of 1 microliter. caused an almost immediate rise in tail skin temperature and a concomitant fall in core temperature in the conscious rat maintained at an ambient temperature of 17 +/- 1 degrees C. 2. The location of the dopamine-sensitive site was defined more accurately by reducing the dose volume to 0.5 microliter. and injecting dopamine at different points throughout the preoptic and anterior hypothalamic region. 3. The largest mean fall in core temperature (1.13 +/- 0.22 degrees C) was obtained after injection into the preoptic region. Injections with their perimeters more than 0.4 mm rostral or caudal to this site were ineffective. 4. Rats placed 0.65 m below a 250 W infra-red lamp responded to the imposed heat load by vasodilation of the tail skin blood vessels, indicated by an increased tail skin temperature. 5. Bilateral, but not unilateral, injection of either pimozide (0.5 microgram) or haloperidol (2.5 microgram) into the preoptic region significantly reduced the increase in tail skin temperature so that the rats were less able to withstand the imposed heat load. 6. Three serial sections (0.5 mm thick) were prepared from the preoptic anterior hypothalamic region of the rat brain, one anterior, one posterior and one corresponding to the dopamine-sensitive site. 7. Tissue from the middle slice increased its rate of synthesis of 3,5-cyclic AMP in response to addition of dopamine 20 or 100 micron to the incubation medium. The posterior slice was inactive, but the anterior slice had similar activity to the middle slice. 8. The effect of dopamine on the middle slice was specifically blocked by haloperidol (0.1 micron), whereas the effects on the anterior slice were partially blocked by both haloperidol (0.1 micron) and propranolol (0.1 micron). 9. These results indicate that there is within a well defined area of the preoptic region a population of dopamine receptors, which play a part in the transmission of information from warm sensors to heat loss effectors.

Animals↗
PubMed1978

Is acetylcholine involved in a dopamine receptor mediated hypothermia in mice and rats?

1 Apomorphine and oxotremorine caused a dose-related fall in core temperature in the mouse and a fall in core temperature preceded by an increase in tail-skin temperature in the rat.2 In both species the slope of the dose-response curve was greater for oxotremorine (8.2 +/- 0.6 mice, 0.9 +/- 0.1 rats) than it was for apomorphine (1.7 +/- 0.3 mice, 0.5 +/- 0.07 rats).3 The mouse was more sensitive than the rat to the effects of both agonists.4 Atropine (0.625 to 5 mg/kg) and hyoscine (0.5 and 1 mg/kg) caused a dose-related rightward shift of the dose-response curve to oxotremorine in mice, but pimozide (0.25 to 1 mg/kg) was ineffective. Similar results were obtained in the rat.5 Pimozide (0.125 to 1 mg/kg) caused a dose-related rightward shift of the dose-response curve to apomorphine in mice, but atropine (1.25 to 1 mg/kg) and hyoscine (0.5 and 1 mg/kg) were ineffective. Similar results were obtained in the rat.6 Intrahypothalamic injection of apomorphine (10 mug) and oxotremorine (1.25 mug) caused a fall in core temperature in rats. Pimozide (0.5 mg/kg i.p.) caused reversal of the effect of apomorphine but did not significantly change the response to oxotremorine. Atropine (2.5 mg/kg i.p.) blocked the effect of oxotremorine, but not that of apomorphine.7 These results suggest that there are both central dopamine and central muscarinic acetylcholine receptors which mediate a fall in core temperature in rodents, but do not support the hypothesis that any connection exists between these two receptor populations.

Acetylcholine↗
PubMed1977

Do central dopamine receptors have a physiological role in thermoregulation?

1 Core and tail skin temperature was measured in rats which had guide cannulae implanted into their brains to allow drug injections directly into the preoptic anterior hypothalamus. 2 Apomorphine and dopamine (10 microgram in 1 microliter) injected into the area of the preoptic anterior hypothalamus caused a fall in core temperature which was preceded by a rise in tail skin temperature. 3 The decrease in core temperature following central injection of either apomorphine or dopamine was significantly reduced by pretreating rats for 2 h with pikozide 0.5 mg/kg i.p.). 4 Bilateral intrahypothalamic injection of pimozide (0.5 microgram in 1 microliter) significantly reduced the hypothermic effect of systemic apomorphine (1.25 mg/kg i.p.). 5 Control rats placed 65 cm below a 250 W infrared lamp responded with vasodilation of tail skin blood vessels as indicated by an increase in tail skin temperature. Pimozide pretreatment (0.5 mg/kg i.p.) significantly reduced this response. 6 These results suggest that the preoptic anterior hypothalamus contains dopamine receptors which mediate hypothermia in rodents and raise the possibility that endogenous dopamine has a physiological role in thermoregulation.

Animals↗