Recent studies have revealed that the administration of purified endotoxins derived from Gram-negative bacilli, or of cellular components of mycobacteria, can increase in a lasting manner the resistance of mice to various types of heterologous bacterial infections (1-5).There is evidence that the activity of endotoxins in this regard is associated with a component which has been designated as "Lipid A" (6, 7) and is related to the sequence of hydrophobic and hydrophilic groups in the molecule of this lipide (8). It is also known that certain types of infection modify resistance to heterologous microbial agents, but this aspect of the problem will not be considered here.Administration of endotoxins has many other physiological effects in mice. It can bring about an increase of phagocytic activity of white blood cells (9), an activation of the properdin system (10), a stimulation of the hypophyseal-adrenal complex (11,12), and profound changes in the so called reticulo-endothelial system (RES) 1 (13). Other physiological alterations have been recognized in higher animals as well as in man (14-16).Of special relevance to the present study are the findings which bear on the phagocytic activity of the RES (17-19). In brief, it can be said that the change in phagocytic activity of this system elicited either by infection with Gram-negative bacilli, or by injection of their toxins, is conditioned by the species and age of the animal, by the rate of blood flow through the liver, and by the characteristics and amounts of the infectious agent or of the endotoxin (20). The change in phagocytic activity follows in general a fairly characteristic pattern. There is first a phase of decreased activity, followed by a positive phase which reaches a maximum 3 to 5 days after treatment or infection. Phagocytic activity then progressively decreases, reaching a normal level around the 7th to 9th day. In fatal infections, needless to say, the activity of the RES falls to a subnormal level some time before death.In animals which have been treated with a protective dose of endotoxin the injection of bacteria elicits a stimulation of the RES more pronounced than that elicited by either infection, or endotoxin alone. In this case again, phagocytic activity does 1 The expression RES is used here with full awareness of its ambiguity. In the present study the RES is defined in terms of a particular activity,--namely the uptake of carbon particles. 523
Abstract— Using a sensitive and specific fluorometric procedure involving selective extraction, reaction of the extracts with o‐phthalaldehyde (OP), separation of the OP derivatives by TLC, and determination of fluorescent characteristics and intensities, we have detected and measured 5‐methoxytryptamine, (5‐MT) in various central and peripheral tissues and fluids of the rat, dog, baboon, and man. Distribution of 5‐MT in peripheral tissues of the rat seemed to parallel that of 5‐HT, with highest levels being found in the gastrointestinal (GI) tract and Harderian gland, regions that are rich in 5‐HT and have been reported to contain systems capable of methylating 5‐HT. 5‐MT was detected in the lung, plasma, kidney, spleen, and heart of the rat. 5‐MT was present in the CNS of all species examined. No marked interspecies differences were observed. In the rat CNS, the regional distribution of 5‐MT did not parallel that of 5‐HT indicating that the systems for the synthesis, uptake, or transport of 5‐MT might be different than for 5‐HT. Pretreatment of rats with iproniazid resulted in a 50% increase in whole brain 5‐MT. Reserpine pretreatment had no effect, indicating that the storage or release mechanisms for 5‐MT are different than for the conventional amine transmitters. 5‐MT was detected in human CSF and urine but not in plasma. These data indicate that 5‐MT, a compound with potent pharmacological properties, is more widely distributed in the mammalian body than had previously been supposed.
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