Bill A. Williams

Hypothermic and antipyretic effects of ACTH (1-24) and alpha-melanotropin in guinea-pigs

Abstract Intracerebroventricular administration of adrenocorticotropin (ACTH 1–24) and α-melanotropin (α-MSH), peptides which occur naturally in brain induced dose-related hypothermia in guinea-pigs at room temperature (21°C) and also produced greater hypothermia at low (10°C) ambient temperature. However, when the experiments were repeated in a warm (30°C) environment, no effect on body temperature was observed. These results indicate that the peptides did not reduce the central set-point of temperature control. The hypothermia induced by ACTH and α-MSH was not mediated via histamine H 1 - or H 2 -receptors and serotonin since the H 1 -receptor antagonist, mepyramine, the H 2 -receptor antagonist, cimetidine, and the serotonin antagonist, methysergide, had no antagonistic effects. The peptides were antipyretic since they reduced pyrogen-induced-fever and hyperthermia due to prostaglandin E 2 , norepinephrine and dibutyryl cAMP, at a dose which did not affect normal body temperature. The powerful central effects of these peptides on normal body temperature, fever and hyperthermia, together with their presence of the brain regions important to temperature control, suggest that they participate in thermoregulation.

Effect of ambient temperature on the thermal profile of the human forearm, hand, and fingers

Forearm, hand, and finger skin temperatures were measured on the right and left sides of seven resting men. The purpose was to determine the bilateral symmetry of these segmental temperature profiles at ambient temperatures from 10 to 45°C. Thermistors placed on the right and left forearms, hands, and index fingers were used to monitor the subjects until equilibration was reached at each ambient temperature. Additionally, thermal profiles of both hands were measured with copper-constantan thermocouples. During one experimental condition (23°C ambient), rectal, ear canal, and 24 skin temperatures were measured on each subject. Average body and average skin temperatures are given for each subject at the 23°C ambient condition. Detailed thermal profiles are also presented for the dorsal, ventral, and circumferential left forearm, hand, and finger skin temperatures at 23°C ambient. No significant differences were found between the mean skin temperatures of the right and left contralateral segments at any of the selected ambient temperatures.

Hyperthermic responses to central injections of some peptide and non-peptide opioids in the guinea-pig

Intracerebroventricular administration of prototype non-peptide opioid receptor (mu, kappa, sigma) agonists, morphine, ketocyclazocine and N-allyl normetazocine (SKF 10,047) and an agonist at both kappa and sigma receptors, pentazocine, induced hyperthermia in guinea-pigs. Similar administration of peptide opioids like beta-endorphin (BE), methionine enkephalin (Met-E), leucine enkephalin (Leu-E) and their synthetic analogues D-ala2-methionine-enkephalinamide (D-ala2-Met-E) and D-ala2-leucine-enkephalinamide (D-ala2-Leu-E) also caused hyperthermia. Of the three anion transport systems (iodide, hippurate and liver-like) present in the choroid plexus, only the liver-like transport system seems to be important to central inactivation of beta-endorphin, D-ala2-Met-enkephalin and D-ala2-Leu-enkephalin since iodipamide (an inhibitor of the liver-like transport system) augmented the hyperthermia. Prostaglandins (PG) and norepinephrine (NE) were not involved in peptide- and non-peptide opioid-induced hyperthermia because a prostaglandin synthesis inhibitor, indomethacin, and an alpha-adrenergic receptor blocker, phenoxybenzamine, had no thermolytic effect. Likewise cAMP was not required since a phosphodiesterase inhibitor, theophylline, did not accentuate the hyperthermia due to administration of peptide and non-peptide opioids. Naloxone-sensitive receptors were involved in the induction of hyperthermia by morphine and beta-endorphin since naloxone attenuated the effect. In contrast, the hyperthermic responses to ketocyclazocine, SKF 10,047, pentazocine, Met-enkephalin, Leu-enkephalin, D-ala2-Met-enkephalin and D-ala2-Leu-enkephalin were not antagonized by naloxone. Lack of antagonism of naloxone on pyrogen, arachidonic acid, PGE2, dibutyryl cAMP and NE-induced hyperthermia indicates that endogenous opioid peptides are not likely to be central mediators of the hyperthermia induced by these agents.

Peptide and non-peptide opioid-induced hyperthermia in rabbits.

Intracerebroventricular administration of all three prototype non-peptide opioid receptor (mu, kappa and sigma) agonists, morphine, ketocyclazocine and N-allyl-normetazocine (SKF 10,047) induced hyperthermia in rabbits. Similar administration of peptide opioids like beta-endorphin (BE), methionine-enkephalin (ME) and its synthetic analogue D-ala2-methionine-enkephalinamide (DAME) also caused hyperthermia. As expected, the synthetic enkephalin DAME was more potent than the parent enkephalin. Of the three anion transport systems (iodide, hippurate and liver-like or L) present in the choroid plexus, it is suggested that only the L transport system seems to be important to ventricular inactivation of BE and DAME since iodipamide (an inhibitor of the L transport system) augmented the hyperthermia produced by BE and DAME. Prostaglandins (PG) and norepinephrine (NE) were not involved in peptide and non-peptide opioid-induced hyperthermia because a PG synthesis inhibitor, indomethacin, and an alpha-adrenergic receptor blocker, phenoxybenzamine, had no thermolytic effect on them. Likewise cAMP was not required since a phosphodiesterase inhibitor, theophylline, did not accentuate the hyperthermia due to peptide and non-peptide opioids. Naloxone-sensitive receptors were involved in the induction of hyperthermia by morphine. BE, ME and DAME since naloxone attentuated them. In contrast, the hyperthermic response to ketocyclazocine and SKF 10,047 were not antagonized by naloxone.

Biogenic amines and acute thermal stress in the rat

Abstract 1. 1. Rats pretreated with biogenic-amine depleting agents demonstrated significant alterations in rectal temperatures ( T re ) in response to 1 hr of acute thermal stress. 2. 2. Depletion of norepinephrine (NE) caused a significant depression of equilibrium T re at 22°C and a greater depression of T re than controls in response to cold (6°C) stress. NE depletion also caused a significantly higher T re response to an acute heat (38°C) stress. 3. 3. Animals in which 5-hydroxytryptamine (5-HT) was depleted showed no significant difference in equilibrium T re at 22°C, and no significant difference in T re during cold stress, but a lesser rise in T re in the heat stress when compared to control animals. 4. 4. Simultaneous depletion of NE and 5-HT caused thermoregulatory responses et equilibrium and at 38°C similar to those produced by depletion of NE. 5. 5. It appears that normal thermoregulation during acute temperature stress may be disrupted by pharmacologic agents which deplete NE and 5-HT but it is still unclear whether the primary site of action of these agents is central or peripheral.

Central effects of dibutyryl cyclic AMP and GMP on the temperature in conscious rabbits.

Intracerebroventricular (i.c.v.) administration of dibutyryl cyclic AMP (Db-cAMP)- and dibutyryl cyclic GMP (Db-cGMP)-induced hyperthermia in rabbits. Central administration of 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone (ZK 62711), a selective inhibitor of cAMP phosphodiesterase, only accentuated the hyperthermia due to Db-cAMP whereas a selective inhibitor of cGMP phosphodiesterase, 2-O-proproxyphenyl-8-azapurin-6-one (M and B 22948), only potentiated the hyperthermia caused by Db-cGMP. The hyperthermia due to Db-cAMP and Db-cGMP was not mediated through prostaglandins (PG). In contrast, central administration of an alpha-adrenergic receptor antagonist, phenoxybenzamine, or a beta-adrenergic receptor antagonist, sotalol, only attenuated the hyperthermic response to Db-cAMP while a cholinergic muscarinic receptor antagonist, atropine, specifically antagonized Db-cGMP-induced hyperthermia. I.c.v. administration of a protein synthesis inhibitor, anisomycin, did inhibit the hyperthermia due to Db-cAMP and Db-cGMP. Opiate antagonist, naloxone, did not antagonize Db-cAMP- and Db-cGMP-induced hyperthermia. These results suggest that a protein mediator is implicated in the induction of hyperthermia by Db-cAMP and Db-cGMP and that cAMP and cGMP may be involved through alpha/beta-adrenergic and cholinergic muscarinic receptors respectively in the central regulation of heat production/conservation in rabbits.

Ca2+ induced hypothermia in a hibernator (Citellus beechyi)

Abstract 1. 1. Excess Ca2+ and Na+ were perfused into the preoptic anterior hypothalamus (POAH) and the posterior hypothalamus (PHYPO) of adult, awake ground squirrels, Citellus beechyi, at high (33°C), low (12°C) and neutral (25°C) temperatures. 2. 2. Excess Na+ results in a moderate rise of core temperature only when perfused into the PHYPO 3. 3. Excess Ca2+ results in respiratory and heart rate decreases, partial loss of thermoregulatory control and general depressant effects when perfused into either region. The magnitude of the effects of hypothalamic Ca2+ perfusion on core temperature are determined by dose, but also by air temperature since Ca2+ perfusion causes a greater drop in core temperature at lower ambient temperatures and even causes a rise in core temperature at high ambient temperatures. 4. 4. Ca2+ perfusion into the hypothalamus of ground squirrels apparently causes a non-specific depression of thermoregulatory control and does not determine the “set-point” for thermoregulation.

Opposing actions of dibutyryl cyclic AMP and GMP on temperature in conscious guinea-pigs

Intracerebroventricular administration of dibutyryl cyclic AMP (Db-cAMP), induced hyperthermia in guinea-pigs which was not mediated through prostaglandins (PG) or norepinephrine since a prostaglandin synthesis inhibitor, indomethacin, and an alpha-adrenergic receptor blocking agent, phenoxybenzamine did not antagonize the hyperthermia. In contrast, the hyperthermic response to dibutyryl cyclic AMP was attenuated by central administration of a beta-adrenergic receptor antagonist, sotalol, indicating that cyclic AMP may be involved, through beta-adrenergic receptors, in the central regulation of heat production/conservation. Central administration of dibutyryl cyclic GMP (Db-cGMP) produced hypothermia which was not mediated via histamine H1- or H2-receptors and serotonin since the H1-receptor antagonist, mepyramine, the H2-receptor antagonist, cimetidine, and the serotonin antagonist, methysergide, had no antagonistic effects. The antagonism of hypothermia induced by dibutyryl cyclic GMP and acetylcholine + physostigmine, by central administration of a cholinergic muscarinic receptor antagonist, atropine, and not by a cholinergic nicotinic receptor antagonist, d-tubocurarine, suggests that cholinoceptive neurons and endogenous cyclic GMP may regulate heat loss through cholinergic muscarinic receptors. These results support a regulatory role in thermoregulation provided by a balance between opposing actions of cyclic AMP and cyclic GMP in guinea-pigs.

Hyperthermic effects of centrally injected (D-ala2, N-Me-Phe4, Met-(O)5-ol)-enkephalin (FK 33-824) in rabbits and guinea-pigs.

Intracerebroventricular administration of (D-ala2, N-Me-Phe4, Met-(O)5-ol)-enkephalin (FK 33-824) induced dose-related hyperthermia in rabbits and guinea-pigs. Prostaglandins (PG) and norepinephrine (NE) were not involved in the hyperthermia induced by FK 33-824 because a cyclooxygenase inhibitor, indomethacin, and an alpha-adrenoceptor antagonist, phenoxybenzamine, had no antagonistic effects. Likewise, cAMP was not required since a phosphodiesterase inhibitor, theophylline, did not accentuate the hyperthermia due to FK 33-824. It is suggested that mu receptors were involved in the induction of hyperthermia by FK 33-824 in rabbits and guinea-pigs since naloxone attenuated it. These results indicate that FK 33-824-induced hyperthermia is not mediated by PG, NE and cAMP, but rather that mu receptors are involved in the induction of hyperthermia by FK 33-824.

An Electrode System for Tetrapolar Electrical Impedance Plethysmography of the Finger

A rigid band electrode system is described which facilitates location of the recording electrodes of a tetrapolar impedance plethysmograph used for measuring pulsations of blood in a finger segment. The electrodes can be relocated accurately, and the volume of the finger segment under study can be precisely defined. The new system ensures good electrical contact and minimizes movement artifacts in the plethysmograph trace by holding the finger segment in a firm position.