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Query: UMLS:C0043167 (
pertussis
)
19,595
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Oxytocin (OT) induces PG synthesis by both uterine endometrial and amnion cells. We showed previously that CHO cells stably transfected with the rat oxytocin receptor (CHO-
OTR
cells) also synthesize PGE2 in response to OT. In the present work we have demonstrated that OTRs are coupled to both Gi and Gq/11, using immunoprecipitation of solubilized
OTR
complexes and ADP ribosylation. OT treatment caused the rapid phosphorylation of extracellular signal-regulated protein kinase 2 (ERK2 or p42MAPK), which was partially inhibited by
pertussis
toxin (PTX), consistent with
OTR
-Gi coupling. The PTX-insensitive portion of ERK2 phosphorylation was linked to Gq, as inhibitors of both phospholipase C (U-73122) and protein kinase C (GF-109203X) blocked OT-induced ERK2 phosphorylation. OT-stimulated c-fos expression was also mediated by ERK2 phosphorylation. The ERK-c-fos pathway has been shown to be associated with cell proliferation, but OT had no effect on [3H]thymidine uptake by CHO-
OTR
cells. However, inhibition of OT-induced ERK2 phosphorylation with an ERK kinase inhibitor (PD-98059) markedly reduced OT-stimulated PGE2 synthesis, pointing to the importance of ERK2 activation in OT action.
...
PMID:ERK2 mediates oxytocin-stimulated PGE2 synthesis. 957 24
The neurohypophyseal hormone oxytocin (OT) regulates biologic functions in both peripheral tissues and the central nervous system. In the central nervous system, OT influences social processes, including peer relationships, maternal-infant bonding, and affiliative social relationships. In mammals, the nonapeptide OT structure is highly conserved with leucine in the eighth position (Leu
8
-OT). In marmosets (
Callithrix
), a nonsynonymous nucleotide substitution in the
OXT
gene codes for proline in the eighth residue position (Pro
8
-OT). OT binds to its cognate G protein-coupled receptor (
OTR
) and exerts diverse effects, including stimulation (G
s
) or inhibition (G
i/o
) of adenylyl cyclase, stimulation of potassium channel currents (G
i
), and activation of phospholipase C (G
q
). Chinese hamster ovary cells expressing marmoset or human oxytocin receptors (mOTRs or hOTRs, respectively) were used to characterize OT signaling. At the mOTR, Pro
8
-OT was more efficacious than Leu
8
-OT in measures of G
q
activation, with both peptides displaying subnanomolar potencies. At the hOTR, neither the potency nor efficacy of Pro
8
-OT and Leu
8
-OT differed with respect to G
q
signaling. In both mOTR- and hOTR-expressing cells, Leu
8
-OT was more potent and modestly more efficacious than Pro
8
-OT in inducing hyperpolarization. In mOTR cells, Leu
8
-OT-induced hyperpolarization was modestly inhibited by pretreatment with
pertussis
toxin (PTX), consistent with a minor role for G
i/o
activation; however, the Pro
8
-OT response in mOTR and hOTR cells was PTX insensitive. These findings are consistent with membrane hyperpolarization being largely mediated by a G
q
signaling mechanism leading to Ca
2+
-dependent activation of K
+
channels. Evaluation of the influence of apamin, charybdotoxin, paxilline, and TRAM-34 demonstrated involvement of both intermediate and large conductance Ca
2+
-activated K
+
channels.
...
PMID:A Comparison of the Ability of Leu
8
- and Pro
8
-Oxytocin to Regulate Intracellular Ca
2+
and Ca
2+
-Activated K
+
Channels at Human and Marmoset Oxytocin Receptors. 3073 93
