Activation of protein kinase C by oxytocin inhibits the biological activity of the human myometrial corticotropin-releasing hormone receptor at term
UNSPECIFIED. (1999) Activation of protein kinase C by oxytocin inhibits the biological activity of the human myometrial corticotropin-releasing hormone receptor at term. ENDOCRINOLOGY, 140 (2). pp. 585-594. ISSN 0013-7227Full text not available from this repository.
The role of placental CRH in human pregnancy is currently unknown. The myometrium expresses CRH receptors that during pregnancy become coupled to adenylate cyclase. Oxytocin (OT) is one of the main regulators of uterine activity, acting via activation of the inositol triphosphate pathway. In view of the possible cross-talk between the CRH and OT signal transduction pathways we have sought to examine in more detail the second messenger mechanisms involved. CRH receptor binding affinity for CRH and activation of adenylate cyclase were reduced in the presence of OT in pregnant (at term, but not preterm) human myometrium. OT action was mediated via pertussis toxin-sensitive G proteins, which directly inhibit adenylate cyclase and, via activation of protein kinase C, phosphorylate the CRH receptor, leading to desensitization. Activation of protein kinase C by OT could be partially inhibited in human pregnant myometrial cells by OT antagonists (F327 and CAP476; 1 mu M) or phospholipase C inhibitors (U73122; 10 mu M). These results suggest that in term myometrium, CRH receptor function is modulated by OT, leading to reduced biological activity, lower cAMP levels, and a subsequent shift, in favor of contractility rather than relaxation.
|Item Type:||Journal Article|
|Subjects:||R Medicine > RC Internal medicine|
|Journal or Publication Title:||ENDOCRINOLOGY|
|Number of Pages:||10|
|Page Range:||pp. 585-594|
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