The aim of the present study was to investigate the role of cAMP in enhanced IL-10 synthesis in human mononuclear cells. Adrenaline is known to act via the alpha- and beta-adrenergic receptors which are coupled to adenylyl cyclase. The effects of cAMP elevation on IL-10 synthesis were studied at the protein level by ELISA and at the level of mRNA by RT/PCR. In this in vitro model adrenaline enhanced the LPS-induced synthesis of IL-10 with parallel suppression of TNF synthesis. These effects were demonstrated both at the protein level and the level of mRNA. To analyze the role of cAMP we antagonized this effect by application of (Rp)-cAMPS, a diastereomer of adenosine-3',5'-cyclic phosphorothioate, known to inhibit competitively the cAMP-induced activation of protein kinase A. Simultaneous addition of adrenaline and (Rp)-cAMPS led to a reversal of IL-10 synthesis to values induced by LPS stimulation alone. The kinetic analysis in LPS-stimulated mononuclear cells revealed a significant delay of IL-10 synthesis starting after 7 h compared with TNF synthesis which showed the first significant increase at 90 min. Finally, the combination of adrenaline and exogenous IL-10 led to a more pronounced suppression of TNF synthesis after LPS stimulation compared to suppression by IL-10 or adrenaline alone. The present results suggest the role of protein kinase A activation for adrenaline-induced IL-10 synthesis in human mononuclear cells. Additionally, based on the kinetic analysis and further experiments described in the literature, endogenous IL-10 could contribute to the adrenaline-induced suppression of TNF synthesis after prolonged incubation. These in vitro results could explain the suppression of TNF plasma concentration after parallel infusion of LPS and epinephrine compared to LPS infusion alone as has been demonstrated in a first human study.

Adrenergic Agonists↗

PubMedDate not supplied

Clinical evaluation of a new hypolipidemic drug, CIBA 13,437-Su.

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Adult↗

PubMedDate not supplied

The effects of microinjection of neurotensin into the caudate nucleus of the rat brain on the performance and extinction of a conditioned motor reflex.

The studies reported here demonstrate that microinjection of neurotensin into the caudate nucleus of the rat brain facilitated extinction of a conditioned motor reflex with reinforcement provided by drinking. Neurotensin had positive effects on the process of post-extinction inhibition in subsequent experiments. Neurotensin microinjections had no marked effect on the performance of the conditioned reflex, though it weakened the emotional tension of the animals in an "open field" test. It is concluded that the functional importance of neurotensin at the level of the caudate nucleus is associated less with the regulation of motor function than with optimizing the motivational-emotional state of the animal.

Animals↗

PubMedDate not supplied

Parenteral nutrition for 48 months.

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Female↗

PubMedDate not supplied

[Effect of neurotensin injections into caudate nuclei on realization and extinction of conditioned motor reflex in rats].

It was shown that neurotensin microinjections into the caudate nuclei facilitated of a conditioned reflex but not affected its realization. Besides, neurotensin was shown to have a positive aftereffect on extinction. Motor activity of rats in the "open field" was augmented after neurotensin administration. A conclusion was drawn that the functional effect of neurotensin administration into the caudate nuclei is connected with the normalization of the motivational and emotional state of an animal rather than with the regulation of the motor function.

Animals↗

PubMedDate not supplied

[Influence of neurotensin on behavior of rats with lesions in serotonergic neurons].

After serotonergic lesion by administration of 5,7-dihydroxytryptamine into the dorsalis raphe nucleus, effects of neurotensin microinjections into the caudate nucleus and substantia nigra on rat behavior were compared. Serotonergic lesions resulted in motivated excitement of rats manifested as an increase in the number of intersignal motor reactions during realization and, particularly, extinction of thirst conditioned reflex. Neurotensin microinjections into the caudate nucleus facilitated extinction of the conditioned reflex both in operated and control rats, but such microinjection into the substantia nigra facilitated this process only in operated animals. Neurotensin did not change conditioned reflex realization in both groups of animals but decreased emotional excitement of rats in the "open field". The behavioral effects of neurotensin in operated rats are connected with normalization of motivational and emotional states of animals and may be explained by recovery of interaction between the dopamine- and serotonergic systems. It is suggested that the mechanisms of this normalizing effects of neurotensin at the levels of the caudate nucleus and substantia nigra are different and are associated preferentially with its action either on dopamine- or serotonergic structures.

5,7-Dihydroxytryptamine↗