Pyrogen fever in rabbits pretreated withp-chlorophenylalanine or 5,6-dihydroxytryptamine

Summary The hyperthermic effect of a bacterial pyrogen has been studied in rabbits pretreated or not withp-chlorophenylalanine or 5,6-dihydroxytryptamine. The results obtained indicate that a selective reduction of cerebral 5-hydroxytryptamine levels by these drugs do not significantly affect pyrogen hypertermia.     

Lack of pyrogenic tolerance transmission between brain and periphery in the rabbit

Successive injections of lipopolysaccharide (LPS) either intravenously (i.v.) or intracerebroventricularly (i.c.v.) induced pyrogenic tolerance to LPS in rabbits. Tolerance was shown by a decrease of the magnitude of the fever response to repeated doses of LPS, irrespective of the route of pyrogen administration. A significantly greater and more dramatic decrease of the fever index, however, was observed in rabbits made tolerant to pyrogen given i.v. than when the pyrogen was given i.c.v. Transmission of the pyrogenic tolerance between brain and peripheral tissues, however, has not been ascertained.     

Lack of pyrogenic tolerance transmission between brain and periphery in the rabbit

Summary Successive injections of lipopolysaccharide (LPS) either intravenously (i.v.) or intracerebroventricularly (i.c.v.) induced pyrogenic tolerance to LPS in rabbits. Tolerance was shown by a decrease of the magnitude of the fever response to repeated doses of LPS, irrespective of the route of pyrogen administration. A significantly greater and more dramatic decrease of the fever index, however, was observed in rabbits made tolerant to pyrogen given i.v. than when the pyrogen was given i.c.v. Transmission of the pyrogenic toleraance between brain and peripheral tissues, however, has not been ascertained.     

Interaction between the effects of centrally administered arecoline and leucocyte pyrogen on the activity of posterior hypothalamic neurons in the rabbit

Summary In experiments with urethane-anesthetized rabbits, the alteration in the activity of posterior hypothalamic neurons resulting from intracerebroventricular injection of leucocyte pyrogen was attentuated by subsequent administration of arecoline. Atropine failed to alter the neuronal response to leucocyte pyrogen but abolished the effect of arecoline. The neuronal response to arecoline was reversed in the absence of leucocyte pyrogen.     

Interaction between the effects of centrally administered arecoline and leucocyte pyrogen on the activity of posterior hypothalamic neurons in the rabbit

In experiments with urethane-anesthetized rabbits, the alteration in the activity of posterior hypothalamic neurons resulting from intracerebroventricular injection of leucocyte pyrogen was attenuated by subsequent administration of arecoline. Atropine failed to alter the neuronal response to leucocyte pyrogen but abolished the effect of arecoline. The neuronal response to arecoline was reversed in the absence of leucocyte pyrogen.     

Influence of endogenous pyrogen on the cerebral prostaglandin-synthetase system

Summary The biotransformation of arachidonic acid to prostaglandins in vitro is specifically augmented by endogenous pyrogen to a degree depending on the concentration applied, providing that the microsomal fraction of the cerebral cortex is used as prostaglandin-synthetase system. This effect is inhibited by non-steroidal anti-inflammatory agents. These findings are compatible with the hypothesis that prostaglandins might act as mediators of the febrile reaction induced by endogenous pyrogen.     

Absence of endotoxin-fever but not hyperthermia in Brattleboro rats

I.c.v. administration of bacterial endotoxin produced a fever in the Long-Evans rat but not in the Brattleboro rat. Similar administration of arachidonic acid, prostaglandin E2, prostacyclin, dibutyryl cAMP, norepinephrine, morphine and beta-endorphin caused hyperthermia in both Long-Evans and Brattleboro rats. Variable doses of exogenous arginine vasopressin (AVP) when centrally administered with endotoxin caused fever in the Brattleboro rat. It is suggested that AVP may play an important role in the production and release of endogenous pyrogen.     

Über die Stoffwechselwirkung eines Lipopolysaccharids ausEscherichia coli

Summary It has been established that pyrogen causes hyperglycemia and diminution of the lactic acid level in the blood. Inin vitro investigations, oxygen requirements of the liver slices show marked increase. The results are regarded as showing a primary action of the pyrogens on metabolism.     

Course of fever response to repeated administration of sublethal doses of lipopolysaccharides, polyinosinic:polycytidylic acid and muramyl dipeptide to rabbits

The purpose of the present study was to examine the development of tolerance to three structurally dissimilar pyrogens, i.e., lipopolysaccharide (LPS), muramyl dipeptide (MDP) and polyinosinic:polycytidylic acid (poly I:C) in rabbits. The possibility of pyrogenic cross-tolerance among these agents has also been studied. It was observed that repeated injection of sublethal doses of LPS and MDP was connected with the changing of biphasic fever to monophasic. The consequence of this was a drop in the fever index. In contrast to LPS and MDP, the repeated administration of poly I:C did not result in such changes. Successive injections of this pyrogen always evoked biphasic fever. We also demonstrated that pyrogenic cross-tolerance between LPS and MDP did not occur. The cross-tolerance between LPS and MDP did not occur. The cross-tolerance among pyrogens was possible if they originated from the same class, for example endotoxin from Salmonella abortus eq. and endotoxin from Escherichia coli.     

Absence of endotoxin-fever but not hyperthermia in Brattleboro rats

Summary I. c. v. administration of bacterial endotoxin produced a fever in the Long-Evans rat but not in the Brattleboro rat. Similar administration of arachidonic acid, prostaglandin E₂, prostacyclin, dibutyryl cAMP, norepinephrine, morphine and -endorphin caused hyperthermia in both Long-Evans and Brattleboro rats. Variable doses of exogenous arginine vasopressin (AVP) when centrally administered with endotoxin caused fever in the Brattleboro rat. It is suggested that AVP may play an important role in the production and release of endogenous pyrogen.     

Course of fever response to repeated administration of sublethal doses of lipopolysaccharides,polyinosinic: Polycytidylic acid and muramyl dipeptide to rabbits

Summary The purpose of the present study was to examine the development of tolerance to three structurally dissimilar pyrogens, i.e., lipopolysaccharide (LPS), muramyl dipeptide (MDP) and polyinosinic: polycytidylic acid (poly I:C) in rabbits. The possibility of pyrogenic cross-tolerance among these agents has also been studied. It was observed that repeated injection of sublethal doses of LPS and MDP was connected with the changing of biphasic fever to monophasic. The consequence of this was a drop in the fever index. In contrast to LPS and MDP, the repeated administration of poly I:C did not result in such changes. Successive injections of this pyrogen always evoked biphasic fever. We also demonstrated that pyrogenic cross-tolerance between LPS and MDP did not occur. The cross-tolerance between LPS and MDP did not occur. The cross-tolerance among pyrogens was possible if they originated from the same class, for example endotoxin fromSalmonella abortus eq. and endotoxin fromEscherichia coli.     

Thermoadaptive influence on reactivity pattern of vasopressinergic neurons in the guinea pig

In cold-adapted guinea pigs, increased amounts of arginine-vasopressin (AVP) immunoreactive material could be visualized in neurons of the supraoptic and paraventricular nucleus, in fibers projecting to the neurohypophysis and in fiber terminals in the ventral lateral septum and in the amygdala. In warm-adapted animals the reactivity to AVP antiserum was poor in all neuronal structures examined. High AVP-immunoreactivity was accompanied by a reduced febrile response to bacterial pyrogen in cold-adapted guinea pigs.     

Thermoadaptive influence on reactivity pattern of vasopressinergic neurons in the guinea pig

Summary In cold-adapted guinea pigs, increased amounts of arginine-vasopressin (AVP) immunoreactive material could be visualized in neurons of the supraoptic and paraventricular nucleus, in fibers projecting to the neurohypophysis and in fiber terminals in the ventral lateral septum and in the amygdala. In warm-adapted animals the reactivity to AVP antiserum was poor in all neuronal structures examined. High AVP-immunoreactivity was accompanied by a reduced febrile response to bacterial pyrogen in cold-adapted guinea pigs.     

Endogenous pyrogen formation by human blood monocytes stimulated by polyriboinosinic acid:Polyribocytidylic acid

The pyrogenic response to supernatants from human blood monocytes stimulated with polyriboinosinic acid:polyribocytidylic acid (poly I:C) was characteristic of a response to endogenous pyrogen in that it was brief and monophasic, and was destroyed by heating the supernatants at 70°C for 30 min. Pyrogen production was unimpaired when the incubations were carried out in the presence of cycloheximide (50 g/ml; an inhibitor of protein synthesis) or indomethacin (50 g/ml; an inhibitor of prostaglandin synthesis). Also, neither interferon, interleukins, tumor necrosis factor nor prostaglandin E₂ were detectable in the supernatants from the poly I:C-stimulated human monocytes.     

The enteric neural receptor for 5-hydroxytryptamine

An enteric neural receptor for serotonin (5-HT) has been characterized. This receptor was assayed, using 3H-5-HT as a radioligand, by rapid filtration of isolated enteric membranes and by radioautography. In addition, intracellular recordings were made from ganglion cells of the myenteric plexus. High affinity, saturable, reversible, and specific binding of 3H-5-HT was demonstrated both to membranes of the dissected longitudinal muscle with adherent myenteric plexus and the mucosa-submucosa. Radioautographs showed these 3H-5-HT binding sites to be in myenteric ganglia and in a broad unresolved band at the mucosal-submucosal interface. Antagonists active at receptors for other neurotransmitters than 5-HT, at either of the two known types of CNS 5-HT receptor, and at 5-HT uptake sites on serotonergic neurons failed to inhibit binding of 3H-5-HT. The structural requirements of analogues for binding to the enteric 5-HT receptor matched the known pharmacology of M or neural 5-HT receptors. A novel 5-HT antagonist was found. This compound, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP), antagonized the action of 5-HT on type II/AH cells of the myenteric plexus but did not affect the release or actions of acetylcholine (nicotinic or muscarinic) or substance P. 5-HTP-DP was also an equally potent displacer of 3H-5-HT from its binding sites on enteric membranes. It is concluded that the sites responsible for specific binding of 3H-5-HT are enteric M or neural 5-HT receptors. These receptors differ from those now known to be present in the CNS.     

Is glucagon involved in cold acclimatization?

Cold acclimatization in rats at 5 degrees C for 2 weeks caused a significant elevation of plasma glucagon concentration, accompanied by increased plasma FFA and glucose levels. Acute cold exposure at 5 degrees C for 5 or 60 min did not affect these parameters in plasma.     

Serotonin levels in fish brain: Effects of hydrostatic pressure and water temperature

Summary The contents of serotonin (5 HT) and its metabolite 5 hydroxy indoleacetic acid (5 HIAA) have been measured (HPLC technique) in the brains of eels exposed to different conditions of hydrostatic pressure and temperature (HP=1 or 101 ATA in winter, Tw=14°C, and in summer, Tw=19°C). It appears that an increase of Tw induces a significant increase of the 5 HT/5 HIAA ratio. In contrast, eels exposed at 101 ATA of HP for 1 h do not exhibit any modification in the 5 HT/5 HIAA brain ratio at a given temperature. The involvement of 5 HT under the conditions studied is discussed.     

Demonstration of a tryptaminergic mechanism in the rat beta-cell.

Yellow 5-HT fluorescence has been histochemically demonstrated in rat pancreatic islet cells in animals injected with L-5-HTP with or without pretreatment with the monoaminoxidase inhibitor nialamide. This fluorescence was not observed after inhibition of the aromatic amino acid decarobxylase. The results strongly suggest the presence of a tryptaminergic mechanism in the rat islet cells.     

Insomnia induced by P-chlorophenylalanine in cats. Its reversibility by intraventricular injections of indolamines

Intraventricular injection of 250 microgram of 5 HTP induces both slow wave and paradoxical sleep, after 20-60 min. latencies, in insomniac Cats pretreated with P-chlorophenylalanine. Direct injections of 5 HTP in several brain stem structures do not induce sleep. The long latency or paradoxical sleep induction and its suppression with chloramphenicol suggest that indolamines are not directly responsible for paradoxical sleep, but that they act by controlling the synthesis and/or the liberation in the periventricular system of some specific paradoxical sleep inducing factor.     

The enteric neural receptor for 5-hydroxytryptamine

Summary An enteric neural receptor for serotonin (5-HT) has been characterized. This receptor was assayed, using³H-5-HT as a radiologand, by rapid filtration of isolated enteric membranes and by radioautography. In addition, intracellular recordings were made from ganglion cells of the myenteric plexus. High affinity, saturable, reversible, and specific binding of³H-5-HT was demonstrated both to membranes of the dissected longitudinal muscle with adherent myenteric plexus and the mucosa-submucosa. Radioautographs showed these³H-5-HT binding sites to be in myenteric ganglia and in a broad unresolved band at the mucosal-submucosal interface. Antagonists active at receptors for other neurotransmitters than 5-HT, at either of the two known types of CNS 5-HT receptor, and at 5-HT uptake sites on serotonergic neurons failed to inhibit binding of³H-5-HT. The structural requirements of analogues for binding to the enteric 5-HT receptor matched the known pharmacology of M or neural 5-HT receptors. A novel 5-HT antagonist was found. This compound, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP), antagonized the action of 5-HT on type II/AH cells of the myenteric plexus but did not affect the release or actions of acetylcholine (nicotinic or muscarinic) or substance P. 5-HTP-DP was also an equally potent displacer of³H-5-HT from its binding sites on enteric membranes. It is concluded that the sites responsible for specific binding of³H-5-HT are enteric M or neural 5-HT receptors. These receptors differ from those now known to be present in the CNS.