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

Chronic treatment with olanzapine causes desensitization of serotonin 2A receptor signaling. The purpose of the current study was to further understand the mechanisms underlying this desensitization response of serotonin 2A receptor signaling in vivo. We report that desensitization of serotonin 2A receptor stimulated-phospholipase C activity in rat frontal cortex induced by olanzapine is dependent on the activation of the JAK-STAT pathway. Olanzapine treatment for 7 days significantly increased the levels of the regulator of G protein signaling (RGS7) protein, RGS7 mRNA levels, and activation of JAK2 in rat frontal cortex. Pre-treatment with a JAK2 inhibitor AG490, significantly attenuated the olanzapine-induced reductions in serotonin 2A receptor-stimulated phospholipase C activity and prevented the olanzapine-induced increases in RGS7 mRNA and protein levels. In contrast, inhibition of the JAK-STAT pathway with AG490 did not reverse the olanzapine-induced desensitization of the serotonin 2A receptor pathway in the hypothalamic paraventricular nucleus mediating increases in plasma hormone levels. AG490 dose-dependently inhibited serotonin 2A receptor-stimulated oxytocin and corticosterone release. These results suggest that the olanzapine-induced increase in RGS7 expression is mediated by the activation of JAK-STAT and is necessary for olanzapine-induced desensitization of serotonin 2A receptor-stimulated phospholipase C activity in the frontal cortex but not serotonin 2A receptor-stimulated hormone release.
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PMID:Activation of the JAK-STAT pathway by olanzapine is necessary for desensitization of serotonin2A receptor-stimulated phospholipase C signaling in rat frontal cortex but not serotonin2A receptor-stimulated hormone release. 1930 67

A 32-year-old primipara, who had been diagnosed as schizophrenia for a year and with good control of the disease by olanzapine administration, requested epidural labor analgesia. Olanzapine is an atypical antipsychotic, and is contraindicated to use with epinephrine, because the a receptor antagonistic action of olanzapine decreases the blood pressure in combination with epinephrine. Hypotention is one of the major complications during the labor epidural analgesia. In addition, this patient is at high risk of hypotension under antipsycotic medication. As hypotension leads to placental-fetal circulation insufficiency, extreme attention to prevent hypotension and to preserve uteroplacental blood flow should be paid. Olanzapine was discontinued before two days of the induction. Sufficient hydration with crystalloid was given beforehand to avoid hypotention. Both phenylephrine and norepinephrine were ready for an anticipated hypotention. Oxytocin infusion began after an epidural catheter was placed at L2-3 intervertebral space. She delivered a healthy baby under good pain control. Apgar score of the baby was 9 and 9 at 1 and 5 minutes after birth, respectively. Total volume of infusion was 2000 ml. No mental disturbance was observed during the labor and delivery. The patient and her baby were discharged on the 4th day postpartum.
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PMID:[Epidural labor analgesia for a primipara with schizophrenia]. 2071 39