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)

We investigated the effect of forskolin on Cl- movements across the isolated epithelium of frog skin. With Cl- on both sides, forskolin (50 mumol/l) increased the transepithelial conductance considerably and elicited significant Cl- secretion. Establishing transepithelial Cl- gradients markedly increased the Cl- currents (ICl). During forskolin treatment, the power density spectra (PDS) of the fluctuation in transepithelial current contained a Lorentzian component that depended on the presence of Cl- in the bathing solutions. Mucosal as well as serosal diphenylamine-2-carboxylic acid (DPC; 1 mmol/l) partially depressed ICl as well as the Lorentzian noise component. Microelectrode recordings from cells involved in transepithelial Na+ absorption showed that forskolin activates gated Cl- channels in a cellular pathway in parallel with the Na+-transporting granulosum cells of the frog skin. The activation of the Cl- -dependent currents and Lorentzian noise was rather variable, and adaptation of the animals to solutions that contained 40 or 60 mmol/l NaCl increased the sensitivity to forskolin. In skins of salt-adapted animals, oxytocin (0.1 U/ml) also slightly activated the Cl- pathway. On the other hand, oxytocin and 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate (CPT-cAMP; 1 mmol/l) were without effect in control skins.
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PMID:Forskolin activates gated Cl- channels in frog skin. 247 70

The physiological role of oxytocin (OT) in the kidney is still unclear, although autoradiographic data have shown the existence of OT receptors in the rat kidney. We examined the effect of OT in the microperfused rabbit cortical collecting duct (CCD) by using conventional cable analysis and microscope photometry. On addition of 10(-9) M OT to the bath, the lumen-negative transepithelial voltage (VT) transiently increased and the transepithelial resistance (RT) and the fractional resistance of the apical membrane (FRA) (1st phase) both decreased. After this initial change, the lumen-negative VT gradually decreased below its baseline level and RT and FRA (second phase) both increased. These electrical changes were dose dependent and were prevented by the addition of 10(-5) M amiloride to the lumen. Although responses to OT were not prevented by 10(-9) M arginine vasopressin (AVP) or 10(-6) M of a V1-receptor antagonist (OPC-21268) or V2-receptor antagonist (OPC-31260), they were inhibited by the addition of the specific OT antagonist des-Gly-NH2-[d(CH2)3,Tyr(Me),Thr]OVT. Additional studies of intracellular free calcium ([Ca2+]i) revealed that 10(-8)-10(-6) M OT caused an increase in [Ca2+]i in CCD in a dose-dependent manner. Also, pretreatment with 2 x 10(-8) M bis-(aminophenoxy)ethane-tetraacetic acid-acetoxymethyl ester, an intracellular Ca2+ chelator, abolished the electrical and [Ca2+]i responses to OT. Pretreatment with 5 x 10(-4) M 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (CPT-cAMP) partially prevented the electrical responses to OT, thus reducing the decrease in lumen-negative VT below its basal level and the increase in RT after the 1st phase. These data show that OT affects the apical Na+ conductance of collecting duct cells through OT receptors distinct from the AVP receptors and that the effect of OT may, at least in part, be brought about by a mechanism(s) dependent on the increase in [Ca2+]i and cAMP production.
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PMID:Oxytocin affects apical sodium conductance in rabbit cortical collecting duct. 823 78

Smooth muscle cells isolated from the myometrium of a pregnant woman at term were infected with a replication-defective adenovirus vector expressing the E6/E7 proteins of human papilloma virus 16. A clonal line, PHM1-41, was selected by resistance to Geneticin and examined for maintenance of smooth muscle phenotype and response to oxytocin. The immortalized cell line retained morphological characteristics of proliferating smooth muscle cells in culture for up to 22 passages and has been used for over 2 years. The cells expressed smooth muscle-specific alpha-actin and retained estrogen receptors. Oxytocin receptors were present, as measured by whole cell binding assay using the oxytocin antagonist 125I-d(CH2)5[Tyr-(Me)2,Thr4,-Orn8,Tyr9-NH2] as ligand and oxytocin as competitor. The data were best described by a one-site binding model, with a Kd of 0.36 nM and a binding site concentration of 37 fmol/microgram DNA. PHM1-41 cells responded to oxytocin with an increase in intracellular free calcium (EC50 15 nM) and an increase in phosphatidylinositol turnover. Oxytocin-stimulated phosphatidylinositol turnover was inhibited by preincubation with the cAMP analog CPT-cAMP. This immortalized myometrial cell line should prove useful for studies relating to human myometrial function.
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PMID:Oxytocin-stimulated responses in a pregnant human immortalized myometrial cell line. 882 50

The effects of cAMP on the oxytocin-stimulated increase in phosphatidylinositide turnover and the possible pathways involved were investigated in a human myometrial cell line (PHM1-41) and in COS-M6 cells overexpressing the oxytocin receptor. Preincubation with chlorophenylthio-cAMP (CPT-cAMP), forskolin, or relaxin inhibited oxytocin-stimulated phosphatidylinositide turnover in PHM1-41 cells, and the inhibition was reversed by H-89, a relatively specific protein kinase A inhibitor. Both CPT-cAMP and transiently expressed protein kinase A catalytic subunit inhibited stimulation by oxytocin and carbachol of [3H]inositol 1,3,4-trisphosphate formation in COS-M6 cells expressing oxytocin or muscarinic M1 receptors, respectively. CPT-cAMP also inhibited phosphatidylinositide turnover stimulation by endothelin-1 in PHM1-41 cells, further demonstrating the generality of the cAMP-inhibitory mechanism. Since G betagamma activation of phospholipase Cbeta2 (PLCbeta2) is a suggested target of protein kinase A, the possibility that the oxytocin receptor couples to PLCbeta2 via G alpha(i)G betagamma activation was explored. Western blot analysis of PHM1-41 cells and COS-M6 cells detected PLCbeta1 and PLCbeta3, but not PLCbeta2. In PHM1-41 cells, pertussis toxin reduced the oxytocin-stimulated increase in [3H]inositol 1,3,4-trisphosphate by 53%, and this was reversed completely by H-89. Thus, the inhibitory effect of pertussis toxin may result from an indirect effect of cAMP elevation. These data suggest that receptor/G alpha(q)-coupled stimulation of PLCbeta1 or PLCbeta3 can be inhibited by cAMP through a phosphorylation mechanism involving protein kinase A that does not involve PLCbeta2. In smooth muscle, this mechanism could constitute potentially important cross-talk between pathways regulating contraction and relaxation.
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PMID:Evidence for inhibition by protein kinase A of receptor/G alpha(q)/phospholipase C (PLC) coupling by a mechanism not involving PLCbeta2. 956 32

1. The effects of adenosine on synaptic transmission in magnocellular neurosecretory cells were investigated using whole-cell patch-clamp recordings in acute rat hypothalamic slices that included the supraoptic nucleus. 2. Adenosine reversibly reduced the amplitude of evoked inhibitory (IPSCs) and excitatory (EPSCs) postsynaptic currents in a dose-dependent manner (IC50 approximately 10 microM for both types of current). 3. Depression of IPSCs and EPSCs by adenosine was reversed by the application of the A1 adenosine receptor antagonist 8-cyclopentyl-1, 3-dimethylxanthine (CPT; 10 microM). 4. When pairs of stimuli were given at short intervals, adenosine inhibitory action was always less effective on the second of the two responses than on the first, resulting in an increased paired-pulse facilitation and suggesting a presynaptic site of action. This observation was confirmed by analysis of spontaneous miniature synaptic currents whose frequency, but not amplitude or kinetics, was reversibly reduced by 100 microM adenosine. 5. CPT had no effect on synaptic responses evoked at a low frequency of stimulation (0.05-0.5 Hz), indicating the absence of tonic activation of A1 receptors under these recording conditions. However, CPT inhibited a time-dependent depression of both IPSCs and EPSCs induced during a 1 Hz train of stimuli. 6. Taken together, these results suggest that adenosine can be released within the supraoptic nucleus at a concentration sufficient to inhibit the release of GABA and glutamate via the activation of presynaptic A1 receptors. By its inhibitory feedback action on the major afferent inputs to oxytocin and vasopressin neurones, adenosine could optimally adjust electrical and secretory activities of hypothalamic magnocellular neurones.
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PMID:Adenosine-induced presynaptic inhibition of IPSCs and EPSCs in rat hypothalamic supraoptic nucleus neurones. 1054 29