Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of various agonist and antagonists of dopamine D1 and D2 receptors on lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) production was investigated in mice. Pretreatment of animals with bromocryptine or quinpirole, agonists of dopamine D2 receptors caused a blunting of both the TNF-alpha and NO responses to LPS injected intraperitoneally. Sulpiride, an antagonist of dopamine D2 receptors, decreased the LPS-induced TNF-alpha plasma levels in a dose-dependent manner and inhibited the LPS-induced NO production by peritoneal macrophages. Bromocryptine or quinpirole blunted both the TNF-alpha and NO response to LPS. SCH-23390, an antagonist of dopamine D1 receptors did not alter LPS-induced TNF-alpha production, but inhibited LPS-induced NO production. These results indicate that while the D2 subtype of dopamine receptors is involve in the modulation of both LPS-induced TNF-alpha and NO production, dopamine D1 receptors only regulate the production of NO. Since several drugs possess effect on dopamine D2 receptors, the present observations may be of clinical relevance.
 ...
PMID:Modulation of lipopolysaccharide-induced tumor necrosis factor-alpha and nitric oxide production by dopamine receptor agonists and antagonists in mice. 873 8

Bacterial lipopolysaccharide (LPS) affects pituitary hormone secretion, including prolactin release, by inducing synthesis and release of cytokines such as tumor necrosis factor-alpha (TNF-alpha). Since prolactin is mainly under tonic inhibitory control of dopamine, we investigated the effect of LPS and TNF-alpha on the hypothalamic-pituitary dopaminergic system. LPS (100-250 microg/rat, i.p.) decreased serum prolactin levels after 1 or 3 h. Sulpiride, a dopaminergic antagonist, increased serum prolactin and blocked the inhibitory effect of LPS. LPS increased hypothalamic dopamine and DOPAC concentrations and the DOPAC/dopamine ratio both in mediobasal hypothalamus and the posterior pituitary. LPS also enhanced dopamine and DOPAC concentration in the anterior pituitary. LPS elevated plasma levels of epinephrine, norepinephrine and dopamine but it did not modify the concentration of epinephrine or norepinephrine in the tissues studied. The administration of TNF-alpha (i.c.v., 1 h, 100 ng/rat) decreased serum prolactin but did not affect plasma catecholamine levels. TNF-alpha did not modify the DOPAC/dopamine ratio in hypothalamus or posterior pituitary but increased dopamine and DOPAC concentrations in the anterior pituitary. Incubations of hypothalamic explants showed that TNF-alpha did not modify in vitro basal dopamine release and reduced K(+)-evoked dopamine release. On the contrary, incubations of posterior pituitaries showed that TNF-alpha significantly increased basal and K(+)-evoked dopamine release. These results indicate that LPS and TNF-alpha increase dopamine turnover in the hypothalamic-pituitary axis. This increase in dopaminergic activity could mediate the inhibitory effect of LPS and TNF-alpha on prolactin release. Furthermore, the increase in dopaminergic activity elicited by LPS could be mediated by an increase in hypothalamic TNF-alpha during endotoxemia.
 ...
PMID:Lipopolysaccharide- and tumor necrosis factor-alpha-induced changes in prolactin secretion and dopaminergic activity in the hypothalamic-pituitary axis. 1220 61

The study examined the effect of some typical and atypical antipsychotic drugs on mouse lymphocyte metabolic and proliferative activity in vitro. The typical antipsychotic drug chlorpromazine (3 x 10(-6), 10(-5) and 10(-4) M), significantly inhibited 3H-thymidine incorporation into C57BL/6 mouse spleen cells stimulated by concanavalin A (Con A), lipopolysaccharide (LPS) or pokeweed mitogen (PWM). Chlorpromazine at concentrations of 10(-5) and 10(-4) M also suppressed the metabolic activity of splenocytes after Con A stimulation. The atypical antipsychotic agent clozapine (10(-4) and 10(-5) M) decreased the proliferative activity of splenocytes after LPS stimulation, but its inhibitory effect after Con A was observed only at higher concentrations. On the other hand, clozapine did not affect the metabolic activity of splenocytes. Sulpiride, a selective dopamine D2 antagonist, at concentrations ranging from 10(-8) to 10(-4) M had no inhibitory effect on the proliferative or metabolic activity of the tested cells. The obtained results indicate that of the three antipsychotic drugs studied, chlorpromazine shows the most potent immunosuppressive effect, clozapine produces a moderate effect and sulpiride is totally inactive. These findings suggest that the choice of antipsychotic drugs should also depend on disturbance of immune system activity, in particular, those occurring in the several forms of psychosis.
 ...
PMID:Effect of some antipsychotic drugs on immunoreactivity in C57BL/6 mice. 1286 35