Dopamine uptake by platelets is selective, temperature dependent and not influenced by the dopamine-D1 or dopamine-D2 receptor

The human platelet, which takes up and releases dopamine, has been proposed as a peripheral model for the study of dopaminergic neurons in the central nervous system (CNS). In addition, the platelet has been shown to possess membrane components with pharmacological properties similar to the dopamine-D1 (DA-D1) and D2 (DA-D2) receptor on dopaminergic neurons. We have therefore studied the specificity of the platelet uptake system for dopamine and, as dopamine uptake comprises both internalised and membrane bound dopamine, the contribution of the DA-D1 and DA-D2 receptor to the uptake of dopamine has been assessed. Significant uptake of 3H-dopamine by platelet rich plasma (PRP) occurred after 10 min incubation at 37 degrees C, uptake being maximal after 90 min. In contrast, at 4 degrees C no uptake of 3H-dopamine occurred up to 60 mins incubation but at 20 degrees C was approximately 8% of the 60 min uptake at 37 degrees C. The neurotransmitters serotonin and dopamine inhibited dopamine uptake by platelets in a dose dependent manner. Uptake of dopamine appeared to be via two systems, one of high affinity with low capacity and the other of lower affinity but high capacity. In contrast, noradrenaline, adrenaline, acetylcholine, gamma-aminobutyric acid and histamine (10 microM) had no effect on dopamine uptake by platelets. The DA-D1 receptor antagonist SCH 23390 (10 microns) and the DA-D2 receptor antagonists (10 microM) spiperone, domperidone and (+)-butaclamol did not significantly affect dopamine uptake by platelets. In addition, ouabain and desipramine (100 microM) inhibited dopamine uptake by 21% and 24% respectively whilst reserpine and imipramine (100 microM) increased uptake by 14% and 15%. We therefore conclude that platelets take up dopamine via a selective, temperature dependent mechanism. Our data also suggest that dopamine uptake by platelets does not involve the DA-D1 or DA-D2 receptor.     

The enigma of deep-body thermosensory specificity

Information provided by the analysis of peripheral cold and warm receptors may be considered a useful guide for assessing the specificity of thermal information originating in deep-body tissues. A wealth of data concerning the location of deep-body thermosensors and their neuronal correlates and modes of transduction permits the following theses to be proposed. 1. Unlike the peripheral warm and cold receptors, deep-body thermosensors are only in part represented by afferent fibers, mostly warm sensitive ones that are not character- ized in detail, as the source of thermal information outside the central nervous system (CNS). The more important thermal information generated in the CNS originates mainly from warm-sensitive neurons but contributions of cold-sensitive neurons are not definitely excluded. 2. Unlike the peripheral thermoreceptors, monomodality with respect to natural physical stimuli does not seem to be an essential property of deep-body thermosensors. By contrast, multimodality may underlie at least some of the multitude of interactions between thermoregulatory and other homeostatic control systems. 3. Temperature transduction seems to utilize molecular mechanisms that are also found in neurons that lack any thermosensory functions, and so the transduction mechanisms identified in warm-sensitive CNS neurons do not seem to be specific per se. 4. The observation of a multitude of temperature/response characteristics for thermosensitive CNS neurons has been helpful for categorizing these neurons, but there is no clear information that any one might be particularly relevant. 5. Originating from the peripheral cold and warm receptors two separate but interacting cold- and warm-signal pathways ascend multisynaptically to the hypothalamus as the highest level of thermoregulatory control, and to some extent go further to the sensory cortex. The signal contributed by a deep-body thermosensitive neuron, irrespective of its location, attains specificity by being fed properly into one of the two ascending thermosensory pathways. Received: 25 January 2000 / Accepted: 10 April 2000     

When nonshivering thermogenesis equals maximum metabolic rate: thermal acclimation and phenotypic plasticity of fossorial Spalacopus cyanus (Rodentia)

Many small mammals inhabiting fluctuating and cold environments display enhanced capacity for seasonal changes in nonshivering thermogenesis (NST) and thermoregulatory maximum metabolic rate (MMR). However, it is not known how this plasticity remains in a mammal that rarely experiences extreme thermal fluctuations. In order to answer this question, we determined body mass (m(b)), basal metabolic rate (BMR), NST, MMR, and minimum thermal conductance (C) on a Chilean fossorial caviomorph (Spalacopus cyanus) from a coastal population, acclimated to cold (15 degrees C) and warm (30 degrees C) conditions. NST was measured as the maximum response of metabolic rate (NST(max)) after injection of norepinephrine (NE) in thermoneutrality minus BMR. Maximum metabolic rate was assessed in animals exposed to enhanced heat-loss atmosphere (He-O2) connected with an open-flow respirometer. Body mass and metabolic variables increased significantly after cold acclimation with respect to warm acclimation but to a low extent (BMR, 26%; NST, 10%; and MMR, 12%). However, aerobic scope (MMR/BMR), calculated shivering thermogenesis (ST), and C did not change with acclimation regime. Our data suggest that physiological plasticity of S. cyanus is relatively low, which is in accordance with a fossorial mode of life. Although little is known about MMR and NST in fossorial mammals, S. cyanus has remarkably high NST; low MMR; and surprisingly, a nil capacity of ST when compared with other rodents.     

The effects of dopamine on temperature regulation in goldfish

Summary Microinjections of dopamine (DA) were made into specific forebrain loci in goldfish (Carassius auratus: 40–85 g) to study the involvement of DA in behavioral thermoregulation. Injections of 25, 50, 100 and 250 ng DA into the anterior aspect of the nucleus preopticus periventricularis (NPP) led to consistent, dose-dependent decreases in selected temperature was observed following injections of 5 or 10 ng DA. Injections of the control solution were without effect.Injections of DA into other forebrain loci, including the posterior half of the NPP, either had no thermoregulatory effect or had minor thermoregulatory effects which, in comparison to injections into the most effective sites, were inconsistent and required larger doses to obtain. The decrease in selected temperature following injections of 100 ng DA into the anterior NPP was blocked by haloperidol, a dopaminergic antagonist, but not by phentolamine, a noradrenergic antagonist. Injections of haloperidol alone resulted in a minor, but statistically significant, increase in selected temperature.The most sensitive DA sites lie caudal to the sites most sensitive to norepinephrine within the anterior NPP. DA acts on the dopaminergic receptors of central thermoregulatory neurons in the anterior NPP of goldfish. These receptors appear to mediate behavioral responses to excessively warm environments.Abbreviations DA dopamine - NE norepinephrine - NPP nucleus preopticus periventricularis - PBS phosphate buffer solution     

Localization of the effective thermosensitive site in the preoptic region of the ox.

These studies were carried out using chronically implanted thermode probes in conscious oxen at 15 degrees C air temperature. The probes were perfused with water either 4 degrees C above or 5 degrees C below resiting hypothalamic temperature and the thermoregulatory response measured by the change in auditory meatal temperature during the perfusion periods of 25 or 40 min duration, respectively. The anatomical position of the probes was known relative to the third cerebral ventricle in each animal. The thermosensitive area of the ox anterior hypothalamic/preoptic region was shown to be highly localized in a position corresponding to the posterior part of the area preoptica. The same area was responsible for both warm and cold sensitivity, the warm sensitivity being approximately three times greater than the cold.     

Metabolic and hormonal response to acute cold exposure in newborn pig

Glucose metabolism and changes in plasma insulin, glucagon and catecholamines were studied in unfed newborn pigs during acute cold exposure immediately after birth. When newborn pigs are exposed to a moderate cold external temperature (20 degrees C), they exhibit a transient thermoregulatory response characterized by an increased liver glycogenolysis, an enhanced blood glucose clearance rate (+35%) and a rise in plasma catecholamine concentrations. When the newborn pigs are exposed to a cold external temperature (12 degrees C), they become rapidly (10-12 h after birth) hypothermic and hyperglycaemic. This results from a fall in blood glucose clearance rate (-40%). Muscle glycogenolysis is low in normothermic animals during the 12 h following birth. Muscle glycogenolysis increases after a delay of 6 h in animals exposed to an external temperature of 20 degrees C or 12 degrees C. These data demonstrate that the failure in the thermoregulatory response in the newborn pig exposed to a cold temperature is not the consequence of a lack of mobilization of energy stores, but results from a defect in glucose utilization.     

Thermogenic capabilities of the opossum Monodelphis domestica when warm and cold acclimated: similarities between American and Australian marsupials

1. Monodelphis domestica is a small marsupial mammal from South America. Its thermogenic abilities in the cold were determined when the opossums were both warm (WA) and cold (CA) acclimated. Maximum heat production of M. domestica was obtained at low temperatures in helium-oxygen. 2. Basal metabolic rate (BMR) in the WA animals was 3.2 W/kg and mean body temperature was 32.6 degrees C at 30 degrees C. These values were lower than those generally reported for marsupials. Nevertheless, these M. domestica showed considerable metabolic expansibility in response to cold. Sustained (summit) metabolism was 8-9 times BMR, while peak metabolism was 11-13 times BMR. These maximum values were equal to, or above, those expected in small placentals. 3. Cold acclimation altered the thermal responses of M. domestica, particularly in warm TaS. However, summit metabolism was not significantly increased; nor did M. domestica show a significant thermogenic response to noradrenaline, which in many small placentals elicits non-shivering thermogenesis. The thermoregulatory responses of this American marsupial were, in most aspects, similar to those of Australian marsupials. This suggests that the considerable thermoregulatory abilities of marsupials are of some antiquity.     

Not-adaptive behavior of isotropically heated, inert populations of Oxytricha bifaria (Ciliophora, Stichotrichia)

The physiological effects on isotropically heated populations of Oxytricha bifaria cultured at 24 degrees C were investigated. At 34.6 degrees C ciliates became inert, and did not adaptively react to either cold or warm microgradients; they neither moved towards the favorable cold thermal source nor escaped from the unfavorable warm one. The inert oxytrichas were only able to perform the Side-Stepping Reaction (SSR) on the same spot. However, mobile ciliates at 31.6 degrees C reacted to the cold microgradient by immediately orienting themselves towards its source, without accelerating but reducing their SSR frequency. Moreover, in a warm microgradient such ciliates immediately increased their SSR frequency, then moved away from the thermal source. At 34.6 degrees C the behavior of ciliates was not-adaptive--not acting to guide the organisms to more favorable conditions--whereas at 31.6 degrees C it was still clearly adaptive. Therefore, the locomotory inertness of the oxytrichas at 34.6 degrees C was the result of thermal stress rather than their behavioral response to the environmental isotropy, in contrast to populations of the same species made inert at 9 degrees C.     

Synthetic heat at mild temperatures

"Synthetic heat", also known as the heat grill illusion, occurs when contact with spatially adjacent warm and cold stimuli produce a sensation of "heat". This phenomenon has been explained as a painful perception that occurs when warm stimulation inhibits cold-sensitive neurons in the spinothalamic tract (STT), which in turn unmasks activity in the pain pathway caused by stimulation of C-polymodal nociceptors (CPNs). The "unmasking model" was tested in experiment 1 by combining warm (35-40 degrees C) and cool (> or = 27 degrees C) stimuli that were too mild to stimulate CPNs. After discovering that these temperatures produced nonpainful heat, experiment 2 was designed to determine whether heat could be induced when near-threshold cooling was paired with mild warmth, and whether lowering the base temperature for cooling would increase the noxious (burning, stinging) components of heat for fixed cooling steps of 1-3 degrees C. Cooling by just 1 degrees C from a base temperature of 33 degrees C led to reports of heat on more than 1/3 of trials, and cooling by just 3 degrees C evoked heat on 75% of trials. Lowering the base temperature to 31 or 29 degrees C increased reports of heat and burning but did not produce significant reports of pain. Perception of nonpainful heat at such mild temperatures indicates either that cold-sensitive nociceptors with thresholds very similar to cold fibers innervate hairy skin in humans, or that heat can result from integration of warm fiber and cold fiber activity, perhaps via convergence on nonspecific (e.g., WDR) neurons in the STT.     

Elderly bioheat modeling: changes in physiology,thermoregulation, and blood flow circulation

A bioheat model for the elderly was developed focusing on blood flow circulatory changes that influence their thermal response in warm and cold environments to predict skin and core temperatures for different segments of the body especially the fingers. The young adult model of Karaki et al. (Int J Therm Sci 67:41–51, 2013) was modified by incorporation of the physiological thermoregulatory and vasomotor changes based on literature observations of physiological changes in the elderly compared to young adults such as lower metabolism and vasoconstriction diminished ability, skin blood flow and its minimum and maximum values, the sweating values, skin fat thickness, as well as the change in threshold parameter related to core or skin temperatures which triggers thermoregulatory action for sweating, maximum dilatation, and maximum constriction. The developed model was validated with published experimental data for elderly exposure to transient and steady hot and cold environments. Predicted finger skin temperature, mean skin temperature, and core temperature were in agreement with published experimental data at a maximum error less than 0.5 °C in the mean skin temperature. The elderly bioheat model showed an increase in finger skin temperature and a decrease in core temperature in cold exposure while it showed a decrease in finger skin temperature and an increase in core temperature in hot exposure.     

On the role of the pineal in thermoregulation in the pigeon

Diurnal rhythm in body temperature of pigeons subjected to different experimental conditions (pinealectomized, sham-operated, melatonin-implanted, cold-exposed) was studied under a 12 h light and 12 h dark regimen. The body temperature of pigeons during photophase was higher than that during scotophase in the normal as well as every treatment group studied. Pinealectomized pigeons showed higher body temperature in the photophase as well as scotophase, than that of the normal and sham-operated birds when examined 2 or 3 weeks following the post-surgical acclimatization to 25 or 3 degrees C. However, subcutaneous implantation of melatonin pellets into pinealectomized pigeons nullified or even reversed the hyperthermic effect of pinealectomy. Exposure of pigeons to--18 degrees C for 280 min during photophase as well as scotophase, produced a marked drop in body temperature in pinealectomized, sham-operated and normal pigeons. The pinealectomized pigeons exhibited a higher body temperature than that of the sham-operated and normal ones when exposed to--18 degrees C during the photophase, but not during the scotophase. It was concluded that while the pineal is not necessary for maintaining the daily thermal rhythm in the avian body, it has a thermoregulatory role, in that it prevents rise in body temperature in warm (25 degrees C) acclimatized and chronic cold (3 degrees C) exposed birds. In acute short-term cold (--18 degrees C) exposure however, the temperature regulatory role of the pineal was not effective during the scotophase.     

Effects of cold and capsaicin desensitization on prostaglandin E hypothermia in rats

Intraperitoneal injection of prostaglandin E1 (PGE) produces a transient hypothermia in rats that lasts 1-2 h. Rats exposed to an ambient temperature (Ta) of 26 degrees C displayed a decrease in rectal temperature (Tre) of 0.95 +/- 0.12 degrees C (SE) after injection with PGE (100 micrograms/kg ip). Hypothermia was produced mainly by heat losses, as indicated by increases in tail blood flow. At Ta of 4 degrees C, PGE produced a comparable fall in Tre of 1.00 +/- 0.14 degrees C. However, in the cold the hypothermia was caused solely by decreases in heat production. These results indicate that the PGE-induced hypothermia is not the result of a peripheral vasodilation induced by the direct action of PGE on the tail vascular smooth muscle but is a central nervous system-mediated response of the thermoregulatory system induced by PGE within the peritoneal cavity. Capsaicin injected subcutaneously induces a transient hypothermia in rats because of stimulation of the warm receptors. If administered peripherally in sufficient amounts, it is reputed to impair peripheral warm receptors so that they become desensitized to the hypothermic effects of capsaicin. We measured PGE-induced hypothermias in rats both before and after capsaicin desensitization at Ta of 26 degrees C. Before desensitization the hypothermia was -1.14 +/- 0.12 degrees C, whereas after capsaicin treatment the PGE-induced hypothermia was -0.34 +/- 0.17 degrees C. The biological effects of capsaicin are diverse; however, based on current thinking about the thermoregulatory effects of capsaicin desensitization, our results indicate that peripheral warm receptor pathways are in some manner implicated in the hypothermia induced by intraperitoneal PGE.     

Human morphology and temperature regulation

For nearly a century individuals have believed that there is a link between human morphology and one’s thermoregulatory response in adverse environments. Most early research was focussed on the rate of core cooling in a male adult population and the role of subcutaneous adipose tissue, surface area and the surface-area-to-mass ratio in one’s ability to withstand varying degrees of cold stress. More recently research has addressed heat tolerance in various populations, exploring the role of subcutaneous adipose tissue, surface area and the surface-area-to-mass ratio in one’s ability to maintain thermal equilibrium in warm and hot, dry and humid environments. Since the late 1970s an emphasis has been placed on the role of muscle and muscle perfusion in total-body thermal insulation. Yet, despite the history of research pertaining to human morphology and temperature regulation there is little consensus as to the impact of variations in human morphology on thermoregulatory responses. Individuals differing in body size, shape and composition appear to respond quantitatively differently to variations in both ambient and core temperatures but the interrelations between morphological components and temperature regulation are complex. It is the purpose of this paper to examine the literature pertaining to the impact of variations in muscularity, adipose tissue thickness and patterning, surface area and the surface-area-to-mass ratio on thermoregulation and thermal stability in response to both heat and cold stress. Received: 6 May 1999 / Accepted: 14 July 1999     

Observations on the central mechanism of acetylsalicylate antipyresis.

Leukocytic pyrogen and sodium acetylsalicylate (ASA) were microinjected into the anterior hypothalamus (AH) of urethane anesthetized cats under thermoneutral conditions. The responses of single, identified thermoregulatory neurons in the AH to leukocytic pyrogen placed in the contralateral AH were examined initially. The attempt was then made to determine the effect of ASA on the activity of pyrogen challenged neurons when injected into the AH area opposite to that which received the pyrogen. Stereotaxically located AH units were defined as thermoregulatory by their response to body surface and hypothalamic thermal stimulation; both “thermopositive” (warm) and “thermonegative” (cold) types were studied. Administration of the leukocytic pyrogen was always followed by a change in the discharge rate of the distal thermoregulatory neurons. About half of the units were excited and half were depressed regardless of their thermoresponsive behavior. When ASA was injected after the pyrogen into the opposite AH area, it always altered the neuronal activity and the change was invariably in the direction of the unit's thermal response. The findings indicate that the antipyresis produced by ASA is not due to competition with leukocytic pyrogen for a common receptor site.     

Acclimation of entomopathogenic nematodes to novel temperatures: trehalose accumulation and the acquisition of thermotolerance

The effect of thermal acclimation on trehalose accumulation and the acquisition of thermotolerance was studied in three species of entomopathogenic nematodes adapted to either cold or warm temperatures. All three Steinernema species accumulated trehalose when acclimated at either 5 or 35 degrees C, but the amount of trehalose accumulation differed by species and temperature. The trehalose content of the cold adapted Steinernema feltiae increased by 350 and 182%, of intermediate Steinernema carpocapsae by 146 and 122% and of warm adapted Steinernema riobrave by 30 and 87% over the initial level (18.25, 27.24 and 23.97 microg trehalose/mg dry weight, respectively) during acclimation at 5 and 35 degrees C, respectively. Warm and cold acclimation enhanced heat (40 degrees C for 8h) and freezing (-20 degrees C for 4h) tolerance of S. carpocapsae and the enhanced tolerance was positively correlated with the increased trehalose levels. Warm and cold acclimation also enhanced heat but not freezing tolerance of S. feltiae and the enhanced heat tolerance was positively correlated with the increased trehalose levels. In contrast, warm and cold acclimation enhanced the freezing but not heat tolerance of S. riobrave, and increased freezing tolerance of only warm acclimated S. riobrave was positively correlated with the increased trehalose levels. The effect of acclimation on maintenance of original virulence by either heat or freeze stressed nematodes against the wax moth Galleria mellonella larvae was temperature dependent and differed among species. During freezing stress, both cold and warm acclimated S. carpocapsae (84%) and during heat stress, only warm acclimated S. carpocapsae (95%) maintained significantly higher original virulence than the non-acclimated (36 and 47%, respectively) nematodes. Both cold and warm acclimated S. feltiae maintained significantly higher original virulence (69%) than the non-acclimated S. feltiae (0%) during heat but not freezing stress. In contrast, both warm and cold acclimated S. riobrave maintained significantly higher virulence (41%) than the non-acclimated (14%) nematodes during freezing, but not during heat stress. Our data indicate that trehalose accumulation is not only a cold associated phenomenon but is a general response of nematodes to thermal stress. However, the extent of enhanced thermal stress tolerance conferred by the accumulated trehalose differs with nematode species.     

Integration of temperature and olfactory information in cockroach antennal lobe glomeruli

Individual neurons in the antennal lobe of the cockroach not only respond to warming, cooling and the odor of lemon oil but they also integrate the responses to simultaneously occurring temperature and olfactory stimuli. This integration results in an increase or decrease of the neuron's activity as compared to its responses to the temperature stimuli presented alone. The mean gain for a change in temperature in the warm and cold direction is 9.5 (imp s(-1)) degrees C(-1) and 10.2 (imp s(-1)) degrees C(-1), respectively. Thus, the average neuron elevates its impulse frequency by 1 imp s(-1) when temperature is increased by 0.1 degree C or decreased by 0.09 degree C. Examination of response scatter reveals that the difference required between two warm or two cold stimuli to be discriminated is 0.5 degree C. Similar values for gain and resolving power are obtained for the enhanced responses to the warm-odor and the cold-odor stimulus combinations. The neurons described are: (1) local interneurons innervating a number of glomeruli distributed within the antennal lobe, and (2) projection neurons collecting information from single glomeruli at 140-280 microm from the surface of the antennal lobe and providing links with the calyces of the mushroom bodies and the lateral lobe of the protocerebrum.     

No evidence for bioenergetic interaction between digestion and thermoregulation in Steller sea lions Eumetopias jubatus

The increase in metabolism during digestion--the heat increment of feeding--is often regarded as an energetic waste product. However, it has been suggested that this energy could offset thermoregulatory costs in cold environments. We investigated this possibility by measuring the rate of oxygen consumption of four juvenile Steller sea lions (Eumetopias jubatus) before and after they ingested a meal in water temperatures of 2 degrees-8 degrees C. Rates of oxygen consumption of fasted and fed animals increased in parallel with decreasing water temperature, such that the apparent heat increment of feeding did not change with water temperature. These results suggest that Steller sea lions did not use the heat released during digestion to offset thermoregulatory costs.     

Effect of cold and warm dry air hyperventilation on canine airway blood flow

Tracheobronchial blood flow increases with cold air hyperventilation in the dog. The present study was designed to determine whether the cooling or the drying of the airway mucosa was the principal stimulus for this response. Six anesthetized dogs (group 1) were subjected to four periods of eucapnic hyperventilation for 30 min with warm humid air [100% relative humidity (rh)], cold dry air (-12 degrees C, 0% rh), warm humid air, and warm dry air (43 degrees C, 0% rh). Five minutes before the end of each period of hyperventilation, tracheal and central airway blood flow was determined using four differently labeled 15-micron diam radioactive microspheres. We studied another three dogs (group 2) in which 15- and 50-micron microspheres were injected simultaneously to determine whether there were any arteriovenous communications in the bronchovasculature greater than 15 micron diam. After the last measurements had been made, all dogs were killed, and the lungs, including the trachea, were excised and blood flow to the trachea, left lung bronchi, and parenchyma was calculated. Warm dry air hyperventilation produced a consistently greater increase in tracheobronchial blood flow (P less than 0.01) than cold dry air hyperventilation, despite the fact that there was a smaller fall (6 degrees C) in tracheal tissue temperature during warm dry air hyperventilation than during cold dry air hyperventilation (11 degrees C), suggesting that drying may be a more important stimulus than cold for increasing airway blood flow. In group 2, the 15-micron microspheres accurately reflected the distribution of airway blood flow but did not always give reliable measurements of parenchymal blood flow.     

Physical fitness and thermoregulatory reactions in a cold environment in men

The relationship between the physical fitness level (maximal O2 consumption, VO2max) and thermoregulatory reactions was studied in 17 adult males submitted to an acute cold exposure. Standard cold tests were performed in nude subjects, lying for 2 h in a climatic chamber at three ambient air temperatures (10, 5, and 1 degrees C). The level of physical fitness conditioned the intensity of thermoregulatory reactions to cold. For all subjects, there was a direct relationship between physical fitness and 1) metabolic heat production, 2) level of mean skin temperature (Tsk), 3) level of skin conductance, and 4) level of Tsk at the onset of shivering. The predominance of thermogenic or insulative reactions depended on the intensity of the cold stress: insulative reactions were preferential at 10 degrees C, or even at 5 degrees C, whereas colder ambient temperature (1 degree C) triggered metabolic heat production abilities, which were closely related to the subject's physical fitness level. Fit subjects have more efficient thermoregulatory abilities against cold stress than unfit subjects, certainly because of an improved sensitivity of the thermoregulatory system.