Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to determine whether the previously observed desensitization of hypothalamic 5-hydroxytryptamine1A (5-HT1A) receptors, during daily injections of fluoxetine, is mediated by sustained blockade of 5-HT reuptake. In the present study, we examined the time course effects of another 5-HT uptake inhibitor, paroxetine. Paroxetine reduced the oxytocin, adrenal corticotropic hormone and corticosterone responses to a challenge with the 5-HT1A agonist 8-hydroxy-2-(dipropylamino)tetralin. These reductions in hormone responses were significant after 3 daily injections and reached a maximum after 7 daily paroxetine injections. These hormone responses remained maximally suppressed after 14 daily injections of paroxetine. A single day of paroxetine treatment did not alter the hormone responses to 8-hydroxy-2-(dipropylamino)tetralin. Repeated injections of paroxetine did not reduce the density of 5-HT1A receptors in any brain region but did produce a gradual reduction in the levels of G(i) and G(o) proteins in a region-specific manner. The time course of the paroxetine-induced reduction in the level of G(i1) and G(i3) proteins in the hypothalamus was similar to the effect previously observed with fluoxetine and was also similar to the time course of paroxetine-induced reductions in oxytocin and adrenal corticotropic hormone responses to 8-hydroxy-2-(dipropylamino)tetralin. In conclusion, these results suggest that blockade of 5-HT uptake sites produces a delayed and gradual desensitization of 5-HT1A receptors in the hypothalamus. This desensitization is not due to changes in the density of hypothalamic 5-HT1A receptors. Reduction in the hypothalamic level of G(i3) proteins may play a role in the desensitization of 5-HT1A receptor systems. However, reductions in G(i1) or G(o) proteins cannot be excluded as potential mediators of the desensitization of 5-HT1A receptor systems.
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PMID:A desensitization of hypothalamic 5-HT1A receptors by repeated injections of paroxetine: reduction in the levels of G(i) and G(o) proteins and neuroendocrine responses, but not in the density of 5-HT1A receptors. 931 75

This study investigated the ability of prenatal exposure to cocaine to alter serotonin(2A) (5-HT(2A)) receptor function and paroxetine-induced desensitization of 5-HT(2A) receptor function in rat offspring. Following exposure to saline or (-)cocaine (15 mg/kg, s.c., b.i.d.), during gestational days 13-20, adult male offspring were treated with either saline or paroxetine (10 mg/kg/day, i.p. 14 days). Eighteen hours post-treatment, changes in the stimulation of oxytocin, adrenocorticotropic hormone (ACTH) and corticosterone by (-)4-iodo-2,5-dimethoxyphenylisopropylamine (DOI, 0.5 or 2.0 mg/kg, s.c.) and in 5-HT(2A) receptor densities were determined. Prenatal cocaine exposure did not alter 5-HT(2A) receptor-mediated neuroendocrine responses or 5-HT(2A) receptor densities. In contrast, paroxetine treatment reduced cortical 5-HT(2A) receptors (18-25%) and desensitized 5-HT(2A) receptor-mediated oxytocin responses in both offspring groups. Furthermore, in cocaine offspring, paroxetine produced an inhibition of 5-HT(2A) receptor-mediated increase in plasma ACTH levels and a greater attenuation of the oxytocin responses to (-)DOI. Paroxetine-induced reductions in body weight gain (-8.8%) were comparable in both offspring groups. These data, demonstrating that prenatal exposure to cocaine potentiates paroxetine-induced desensitization of 5-HT(2A) receptor function, may be clinically relevant with respect to treating mood disorders in adults exposed in utero to cocaine.
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PMID:Prenatal cocaine exposure potentiates paroxetine-induced desensitization of 5-HT2A receptor function in adult male rat offspring. 1508 91