Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxytocin receptor (OTR) expression in human myometrium increases over 150-fold from the beginning of pregnancy to the end. In the present studies, we examined potential mechanisms of OTR up-regulation, using myometrial cells in primary culture from women in late gestation. OTR ligand-binding sites and steady-state mRNA levels were down regulated by serum starvation, and up-regulated by restoration of fetal bovine serum (FBS). Transcriptional activity of the OTR gene was the same with or without FBS treatment, but FBS increased OTR mRNA half-life about 5-fold. Lysophospholipids (lysophosphatidic acid and sphingosine 1-phosphate), which are present in serum, had similar effects as FBS. Lysophospholipid receptor mRNAs of the endothelial differentiation gene (Edg) family (Edgs 1, 3, 4, and 5) were demonstrated in myometrial cells by RT-PCR. These G protein-coupled receptors have been shown to be coupled to G(i/o) and to mediate activation of phosphoinositol 3-phosphate kinase. Indeed, the effects of the lysophospholipids and FBS were completely blocked by pertussis toxin, a G(i/o) inhibitor. Likewise, inhibition of G(i/o) signaling by elevation of intracellular cAMP or inhibition of phosphoinositol 3-phosphate kinase blocked FBS effects on OTR mRNA stability. We do not presently understand the mechanisms of OTR up-regulation in human myometrium in vivo, but the present studies might lead to the description of mRNA-stabilizing factors whose activity can be quantified in tissue samples during pregnancy to elucidate the process of OTR up-regulation.
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PMID:Regulation of oxytocin receptor expression in cultured human myometrial cells by fetal bovine serum and lysophospholipids. 1248 30

Oxytocin receptor is a seven transmembrane receptor widely expressed in the CNS that triggers G(i) or G(q) protein-mediated signaling cascades leading to the regulation of a variety of neuroendocrine and cognitive functions. We decided to investigate whether and how the promiscuous receptor/G protein coupling affects neuronal excitability. As an experimental model, we used the immortalized gonadotropin-releasing hormone-positive GN11 cell line displaying the features of immature, migrating olfactory neurons. Using RT-PCR analysis, we detected the presence of oxytocin receptors whose stimulation by oxytocin led to the accumulation of inositol phosphates and to the inhibition of cell proliferation, and the expression of several inward rectifier (IR) K+ channel subtypes. Moreover, electrophysiological and pharmacological inspections using whole-cell patch-clamp recordings evidenced that in GN11 cells, IR channel subtypes are responsive to oxytocin. In particular, we found that: (i) peptide activation of receptor either inhibited or stimulated IR conductances, and (ii) IR current inhibition was mediated by a pertussis toxin-resistant G protein presumably of the G(q/11) subtype, and by phospholipase C, whereas IR current activation was achieved via receptor coupling to a pertussis toxin-sensitive G(i/o) protein. The findings suggest that neuronal excitability might be tuned by a single peptide receptor that mediates opposing effects on distinct K+ channels through the promiscuous coupling to different G proteins.
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PMID:Dual modulation of inward rectifier potassium currents in olfactory neuronal cells by promiscuous G protein coupling of the oxytocin receptor. 2055 24