In vivo adaptative regulation of muscarinic receptors and muscarinic stimulation-induced Ca2+ mobilization during short-term heat exposure in rat parotid glands

1. Adaptation of muscarinic receptors (MR)—muscarinic stimulation—induced intracellular Ca²⁺ mobilization during short-heat exposure (33°C).2. Heat-exposure for 48 hr decreased the carbachol (CCh)-stimulated cytosolic C²⁺ concentration increase.3. The number of MR on cell surface increased transiently at 24 hr with a subsequent decrease at 48 hr.4. CCh-stimulated inositol trisphosphate (IP₃) formation decreased at 48 hr.5. In saponin-permeabilized cells, 1,4,5-IP₃-induced ⁴⁵Ca²⁺ release decreased at 24 hr.6. The data suggest that the adaptation for increased muscarinic stimulation occurs at IP₃ generating sites as well as at intracellular IP₃ receptor sites during heat exposure.     

In vivo adaptive control of beta-receptors and adenylate cyclase during short-term heat exposure in rat parotid glands.

1. Adaptation of beta-adrenergic receptors (beta-AR) and adenylate cyclase (AC) in rat parotid glands during short-term heat exposure (33 degrees C) were studied. 2. Heat exposure reduced AC activity in response to isoproterenol (IPR). 3. The number of beta-AR on the cell surface significantly increased after 24 hr but returned to control level after 48 hr. 4. IPR-induced [3H]GDP release was significantly reduced throughout exposure. 5. The data suggest that the major factor which results in the desensitization of AC during short-term heat exposure is a blunted coupling between beta-AR and GTP binding protein(s).     

Beta 2-adrenoceptor agonist-induced down-regulation after short-term exposure.

We examined the effect of duration of beta 2-adrenergic receptor (beta 2AR) occupancy by isoproterenol on specific binding of 125I-lodocyanopindolol (125I-ICYP) in membranes from rat L6 myoblasts. Ten minute exposure caused a time-and concentration-dependent maximal decrease in 125I-ICYP binding 24 hours after exposure equal to that following continuous exposure (p < 0.05). Low temperature, concanavalin A, H89 and ICl 118,551 blocked the decline in 125I-ICYP binding during the first hour following exposure probably representing receptor sequestration to a compartment or change to a form incapable of ligand binding. Compared to controls, receptor binding 4 and 24 hours following exposure was reduced 56 +/- 8.7% and 72 +/- 8.8%, respectively (p < 0.05), and was blocked by ICl 118,551 but not CGP12177. Isoproterenol-induced, but not forskolin-stimulated, cAMP accumulation was reduced 35% 24 hours following exposure (p < 0.05). 125I-ICYP binding in intact L6 cells 4 and 24 hours after exposure were respectively 56 +/- 8.9 and 61 +/- 13% of controls (p < 0.05). Following agonist exposure, CHO cell membranes expressing human beta 2ARs exhibited 125I-ICYP binding 85 +/- 2.0% and 6 +/- 2.8% of control values 4 and 24 hours, respectively (p < 0.05). A model predicting that full occupation of the beta 2AR activates receptor degradation explains our results that agonist-induced down-regulation of beta 2AR does not require continuous presence of the agonist.     

Effects of short-term exposure to lithium on antiapoptotic Bcl-xL protein expression in cortex and hippocampus of rats after acute stress

The antiapoptotic protein Bcl-xL is involved in development of neurobiological resilience to stress; hence, the possibility of use of psychotropic drugs to increase its expression in brain in response to stress is of considerable interest. Lithium is a neurotropic drug widely used in psychiatry. In work, we studied effects of lithium administration (for 2 or 7 days) on the expression of Bcl-xL mRNA and protein in the hippocampi and cortices of rats subjected to stress that induced depression-like behavior in the animals. In contrast to the brain-derived neurotrophic factor (BDNF), whose expression decreased in the hippocampus in response to acute stress, stress increased the level of Bcl-xL mRNA in the hippocampus, but decreased it in the frontal cortex. Treatment of stressed animals with lithium for 2 or 7 days increased Bcl-xL protein levels 1.5-fold in the hippocampus, but it decreased them in the cortex. Therefore, Bcl-xL expression in the brain can be modulated by both stress and psychotropic drugs, and the effects of these factors are brain region-specific: both stress exposure and lithium administration activated Bcl-xL expression in the hippocampus and suppressed it in the frontal cortex. The activation of Bcl-xL expression in the hippocampus by lithium, demonstrated for the first time in this study, suggests an important role of this protein in the therapeutic effects of lithium in the treatment of stress-induced psychoemotional disorders.     

Thermoregulatory responses to acute body heating in rats acclimated to continuous heat exposure

Thermoregulatory responses to an acute heat load with intraperitoneal heating (IH) or indirect external warming (EW) by increasing ambient temperature (Ta) were investigated with direct and indirect calorimetry in rats acclimated to environments of 24.0 degrees C (Cn), 29.4 degrees C (H1), and 32.8 degrees C (H2) for greater than 15 days. The rats were placed in a direct calorimeter where the air temperature was maintained at 24 degrees C for the initial 3 h. IH was then made for 30 min through an electric heater implanted chronically (6.5 W.kg-1) in the peritoneal cavity, and EW was performed by raising the jacket water temperature surrounding the calorimeter from 24 to 39 degrees C (0.19 degrees C.min-1). Hypothalamic (Thy) and colonic temperature immediately before the start of the heat load tended to be higher as the acclimation temperature increased. During IH, the threshold Thy for the tail skin vasodilation (Tth) was significantly higher in H2 than in Cn rats. During EW, however, there was no difference in Tth between the groups. Metabolic heat production (M) was slightly suppressed during IH and significantly depressed only in H2 rats. During EW, M was suppressed in all the groups. The magnitude and duration of suppression were greater in H2 rats than in the other two groups. The responses in nonevaporative heat loss and thermal conductance (C) to the rise in Thy did not differ among the three groups during IH. According to the rise in Thy, however, there was a greater C increase in H2 than in Cn and H1 rats during EW.(ABSTRACT TRUNCATED AT 250 WORDS)     

Temperature regulation in the unrestrained rabbit during exposure to 600 MHz radiofrequency radiation

Six male New Zealand white rabbits were individually exposed to 600 MHz radiofrequency (RF) radiation for 90 min in a waveguide exposure system at an ambient temperature (Ta) of 20 or 30 degrees C. Immediately after exposure, the rabbit was removed from the exposure chamber and its colonic and ear skin temperatures were quickly measured. The whole-body specific absorption rate (SAR) required to increase colonic and ear skin temperature was determined. At a Ta of 20 degrees C the threshold SAR for elevating colonic and ear skin temperature was 0.64 and 0.26 W/kg, respectively. At a Ta of 30 degrees C the threshold SARs were slightly less than at 20 degrees C, with values of 0.26 W/kg for elevating colonic temperature and 0.19 W/kg for elevating ear skin temperature. The relationship between heat load and elevation in deep body temperature shown in this study at 600 MHz is similar to past studies which employed much higher frequencies of RF radiation (2450-2884 MHz). On the other hand, comparison of these data with studies on exercise-induced heat production and thermoregulation in the rabbit suggest that the relationship between heat gain and elevation in body temperature in exercise and from exposure to RF radiation may differ considerably. When combined with other studies, it was shown that the logarithm of the SAR required for a 1.0 degree C elevation in deep body temperature of the rabbit, rat, hamster, and mouse was inversely related to the logarithm of body mass. The results of this study are consistent with the conclusion that body mass strongly influences thermoregulatory sensitivity of the aforementioned laboratory mammals during exposure to RF radiation.     

Changes in brain enkephalin immunostaining after acute carbon disulfide exposure in rats

Carbon disulfide neurotoxic mechanism in the brain is still not completely clear. In this work, the effect of carbon disulfide exposure in rats on the enkephalinergic neuromodulatory system is described. Caudatus-putamen showed no changes in immunostaining for met-enkephalin when compared with controls. However, a marked reduction in met-enkephalin immunostaining in the central amygdaloid nuclei and the globus pallidus was measured, with a parallel elevation in the lateral septal nucleus and the parietal cortex. It is suggested that enkephalinergic neuromodulatory system could play a role in carbon disulfide neurotoxicity.     

Thermoregulatory responses to acute heat loads in the FOK rat

FOK is an inbred rat strain with a genotypic adaptation to hot environments. The present study investigated the mechanism of the high heat tolerance of the FOK rat. Male FOK and WKAH rats were used. They were loosely restrained and placed individually in a direct calorimeter with an ambient temperature of 24°C. Their hypothalamic temperature, evaporative and nonevaporative heat loss and heat production were measured. After thermal equilibrium had been attained, the rats were warmed for 30 min with a chronically implanted intraperitoneal electric heater(internal heating). At least 90 min after the heating, the jacket water temperature surrounding the calorimeter chamber was gradually raised from 24°C to 36°C in 80 min (external warming). During the internal heating, changes in the thermoregulatory parameters did not differ between the groups. During the external warming, the evaporative heat loss of the FOK rat was significantly greater than that of the WKAH rat, while changes in nonevaporative heat loss and heat production did not differ between the groups. The results suggest that in the FOK rat, the improved heat tolerance is attributable to an enhanced evaporative heat loss response, but not to a facilitation of nonevaporative heat loss or of metabolic depression. Received: 8 March 1999 / Accepted: 14 July 1999     

Stimulation of liver tryptophan pyrrolase during heat exposure.

Exposure of rats to heat (39 +/- 1 degree C) stimulated liver tryptophan pyrrolase 2-fold between 3 and 48 h. Plasma corticosterone increased 2-fold after 1 h of heat exposure and decreased to a low value of 50% by 16 h. The effect of heat exposure on the enzyme was obtained in adrenalectomized animals. Stimulation by cortisol and tryptophan of the enzyme was also obtained in heat exposure, and the effects seemed to be additive. The concentration of tryptophan in the liver remained unchanged, and that in the plasma decreased to about 50% at 8 h exposure to heat and reverted to normal by 46 h. Simultaneous administration of noradrenaline to heat-exposed rats had no effect, whereas that of thyroxine partly prevented the stimulation of the enzyme activity. Hypothyroid conditions obtained by thyroidectomy or treatment with propylthiouracil significantly stimulated the enzyme activity. Cycloheximide treatment of heat-exposed rats did not prevent the stimulation of the enzyme activity. The results indicate that the effect of heat exposure on liver tryptophan pyrrolase is obtained, due to the accompanying hypothyroid condition, by increasing the activity of the existing protein by a mechanism possibly different from those known at present.