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)

Mechanisms regulating uterine contractility are poorly understood. We hypothesized that a specific isoform of small conductance Ca(2+)-activated K(+) (SK) channel, SK3, promotes feedback regulation of myometrial Ca(2+) and hence relaxation of the uterus. To determine the specific functional impact of SK3 channels, we assessed isometric contractions of uterine strips from genetically altered mice (SK3(T/T)), in which SK3 is overexpressed and can be suppressed by oral administration of doxycycline (SK3(T/T)+Dox). We found SK3 protein in mouse myometrium, and this expression was substantially higher in SK3(T/T) mice and lower in SK3(T/T)+Dox mice compared with wild-type (WT) controls. Sustained contractions elicited by 60 mM KCl were not different among SK3(T/T), SK3(T/T)+Dox, and WT mice. However, the rate of onset and magnitude of spontaneously occurring phasic contractions was muted significantly in isolated uterine strips from SK3(T/T) mice compared with those from WT mice. These spontaneous contractions were augmented greatly by blockade of SK channels with apamin or by suppression of SK3 expression. Phasic but not tonic contraction in response to oxytocin was depressed in uterine strips from SK3(T/T) mice, whereas suppression of SK3 channel expression or treatment with apamin promoted the predominance of large coordinated phasic events over tone. Spontaneous contractions and the phasic component of oxytocin contractions were blocked by nifedipine but not by cyclopiazonic acid. Our findings suggest that SK3 channels play an important role in regulating uterine function by limiting influx through L-type Ca(2+) channels and disrupting the development of concerted phasic contractile events.
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PMID:Myometrial expression of small conductance Ca2+-activated K+ channels depresses phasic uterine contraction. 1729 20

Oxytocin (OT) is an endogenous neuropeptide that, while originally thought to promote trust, has more recently been found to be context-dependent. Here we extend experimental paradigms previously restricted to de novo decision-to-trust, to a more realistic environment in which social relationships evolve in response to iterative feedback over twenty interactions. In a randomized, double blind, placebo-controlled within-subject/crossover experiment of human adult males, we investigated the effects of a single dose of intranasal OT (40 IU) on Bayesian expectation updating and reinforcement learning within a social context, with associated brain circuit dynamics. Subjects participated in a neuroeconomic task (Iterative Trust Game) designed to probe iterative social learning while their brains were scanned using ultra-high field (7T) fMRI. We modeled each subject's behavior using Bayesian updating of belief-states ("willingness to trust") as well as canonical measures of reinforcement learning (learning rate, inverse temperature). Behavioral trajectories were then used as regressors within fMRI activation and connectivity analyses to identify corresponding brain network functionality affected by OT. Behaviorally, OT reduced feedback learning, without bias with respect to positive versus negative reward. Neurobiologically, reduced learning under OT was associated with muted communication between three key nodes within the reward circuit: the orbitofrontal cortex, amygdala, and lateral (limbic) habenula. Our data suggest that OT, rather than inspiring feelings of generosity, instead attenuates the brain's encoding of prediction error and therefore its ability to modulate pre-existing beliefs. This effect may underlie OT's putative role in promoting what has typically been reported as 'unjustified trust' in the face of information that suggests likely betrayal, while also resolving apparent contradictions with regard to OT's context-dependent behavioral effects.
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PMID:Oxytocin attenuates trust as a subset of more general reinforcement learning, with altered reward circuit functional connectivity in males. 2948 21