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)

Effects of amiloride analogues on Na transport were studied in isolated skins of the frog Rana ridibunda. The pattern of structure-activity relationship of these compounds showed that both the -NH2 group at position 5 and Cl at position 6 of the pyrazine ring of the amiloride molecule were important for their biological activity. The paramount role of the groups at position 5 was further demonstrated by the striking properties of an analogue resulting from dimethylation of that -NH2 group. A stimulation of Na transport, opposite to the effect of amiloride itself, was observed in this instance. The increase in Na transport could already be seen at 10(-6) M and was equivalent to the measured increase in Na influx, reversible, dose-dependent, and additive to the natriferic action of oxytocin. Such characteristics resemble those reported with "external" agents like propranolol and La3+. Furthermore, mutual inhibition was observed between the stimulatory effects of this analogue and those of propranolol or La3+. These results suggest that the analogue may be considered as another "external" agent acting at sites of the external membrane distinct from those activated by cAMP but similar to the Ca sites described by Herrera and Curran (Herrera, F.C., Curran, P.F. 1963. J. Gen. Physiol. 46:999).
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PMID:Inhibitory and stimulatory effects of amiloride analogues on sodium transport in frog skin. 44 31

1. The effect of (Na+ + K+)-ATPase inhibitor ouabain (10(-5)-3 x 10(-4) M), and the (Ca2+ + Mg2+)-ATPase inhibitors vanadate (6 x 10(-6)-6 x 10(-4) M), oxytocin (2 x 10(-9)-4 x 10(-8) M, and prostaglandin F2 alpha (PGF2 alpha, 10(-7)-6 x 10(-6) M) were assayed on rat uterus incubated in Ca-free medium. 2. Vanadate, oxytocin and PGF2 alpha, but not ouabain, induced contractions in a dose-dependent way (ED50: 7.5 +/- 0.03 x 10(-5) M; 6.5 +/- 0.064 x 10(-9) M and 3.8 +/- 0.085 x 10(-7) M). 3. Vanadate (3 x 10(-4) M) and oxytocin (OT, 10 mU/ml = 2 x 10(-8) M)-induced tonic contraction were not modified by nifedipine (10(-10)-10(-6) M), monensin (10(-5)-3 x 10(-4) M) or amiloride (10(-5)-10(-3) M). 4. The intracellular calcium release inhibitors TMB-8 (10(-6)-10(-4) M) and dantrolene (3 x 10(-6)-10(-4) M), and the prostaglandin release inhibitor indomethacin (3 x 10(-8)-6 x 10(-5) M) relaxed the vanadate and OT-induced tonic contractions. 5. The calmodulin inhibitors trifluoperazine (3 x 10(-5)-3 x 10(-4) M), bepridil (10(-8)-3 x 10(-4) M), calmidazolium (10(-7)-10(-4) M) and W-7 (10(-7)-10(-5) M) also relaxed the vanadate and OT-induced tonic contractions. 6. Our results suggest that oxytocin and vanadate-induced contractions on rat uterus in Ca-free medium could be produced by release of prostaglandins and intracellular calcium, and mediated by calmodulin.
Gen Pharmacol 1992 Mar
PMID:Mediators involved in the rat uterus contraction in calcium-free solution. 132 41

Cerebrospinal fluid hormones, monoaminergic metabolites, and dynorphin A (1-8 sequence) were examined in 43 children with severe, primary obsessive-compulsive disorder. Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid were positively correlated with one of eight obsessive-compulsive disorder severity ratings and three of seven measures of improvement following 5 weeks of treatment with clomipramine hydrochloride. Arginine vasopressin concentration was significantly and negatively correlated with several ratings of obsessive-compulsive disorder symptom severity, while oxytocin concentration was positively correlated with depressive symptoms. The ratio of arginine vasopressin to oxytocin was also negatively correlated with obsessive-compulsive disorder and depressive symptoms. Comorbid affective disorder was associated with decreased arginine vasopressin concentrations, while concomitant anxiety disorder was associated with increased oxytocin. Dynorphin A (1-8 sequence), homovanillic acid, corticotropin, 3-methoxy-4-hydroxyphenylglycol, and corticotropin releasing hormone were not significantly related to obsessive-compulsive disorder symptoms. These results seem to indicate that arginine vasopressin may be related to obsessive-compulsive disorder symptom severity, while 5-hydroxyindoleacetic acid might be associated with drug response.
Arch Gen Psychiatry 1992 Jan
PMID:Cerebrospinal fluid neurochemistry in children and adolescents with obsessive-compulsive disorder. 137 Jan 97

Several morphological and immunochemical characteristics of the neurosecretory neurons of the supraoptic nucleus (SON) have been studied of rats treated for 1 month with D-amphetamine sulfate (AMP) (8 mg/kg weight, daily). An increase of SON volume (11%) has been observed as a consequence of the growth of the dorsoventral axis. Neurosecretory neurons increased their nucleolar area (11.4%), their nuclear area (8.3%), and their cytoplasmatic area (18.3%). Vasopressin immunoreaction did not show any differences between treated and control animals, but oxytocin immunostaining displayed an important increase (23.7%) in the neuronal cytoplasm of the treated rats. The SON hypertrophy of the AMP-treated rats corresponded to the hypertrophy/hyperfunction of its oxytocinergic neurons, and could be considered as a new mechanism of the action of the AMP. The results are discussed in relation to the plastic features of the SON and its central (neuronal) and peripheral (hormonal) function.
J Neural Transm Gen Sect 1992
PMID:Morphometric and neurosecretory changes in supraoptic neurons after D-amphetamine treatment. 141 69

The distribution and properties of nonapeptide binding sites in the kidney of the anuran Xenopus laevis were investigated using quantitative in vitro autoradiography. The binding studies were performed with [3H]arginine vasopressin (AVP) as ligand because [125I]arginine vasotocin (AVT) lacks biological activity. Specific binding sites for [3H]AVP are located in the glomeruli of the kidney. [3H]AVP binding results in a steady state of association and dissociation between ligand and binding sites. Scatchard and Hill analyses of saturation experiments showed that [3H]AVP binds to a single class of binding sites with a dissociation constant (Kd) of 430 +/- 109 pM and a maximum binding capacity (Bmax) of 5.306 +/- 1.379 fmol/mm2 (n = 8). Displacement studies demonstrated the same affinity of these [3H]AVP binding sites to [3H]AVP, unlabeled AVP, and AVT, whereas mesotocin possesses only weak affinity. Further nonapeptides like oxytocin and isotocin or the mammalian-specific V1 receptor antagonist [1-beta-mercapto-beta,beta-cyclopentamethylene propionic acid)-2-(O-methyl)-tyrosine)-AVP or the V2 receptor agonist (1-deamino-8-D-arginine)-vasopressin or unrelated peptides did not alter the binding of [3H]AVP. The localization of nonapeptide binding sites in the glomeruli with the same affinity to AVP as to AVT agrees with the finding that AVT causes antidiuresis in Xenopus laevis. An earlier study demonstrated Xenopus laevis interrenal tissue to possess a higher sensitivity for AVT than AVP which points to a nonapeptide receptor with a higher affinity for AVT than AVP.(ABSTRACT TRUNCATED AT 250 WORDS)
Gen Comp Endocrinol 1992 Jan
PMID:Localization and quantification of nonapeptide binding sites in the kidney of Xenopus laevis: evidence for the existence of two different nonapeptide receptors. 156 20

We have compared the response of proton and water transport to oxytocin treatment in isolated frog skin and urinary bladder epithelia to provide further insights into the nature of water flow and H+ flux across individual apical and basolateral cell membranes. In isolated spontaneous sodium-transporting frog skin epithelia, lowering the pH of the apical solution from 7.4 to 6.4, 5.5, or 4.5 produced a fall in pHi in principal cells which was completely blocked by amiloride (50 microM), indicating that apical Na+ channels are permeable to protons. When sodium transport was blocked by amiloride, the H+ permeability of the apical membranes of principal cells was negligible but increased dramatically after treatment with antidiuretic hormone (ADH). In the latter condition, lowering the pH of the apical solution caused a voltage-dependent intracellular acidification, accompanied by membrane depolarization, and an increase in membrane conductance and transepithelial current. These effects were inhibited by adding Hg2+ (100 microM) or dicyclohexylcarbodiimide (DCCD, 10(-5) M) to the apical bath. Net titratable H+ flux across frog skin was increased from 30 +/- 8 to 115 +/- 18 neq.h-1.cm-2 (n = 8) after oxytocin treatment (at apical pH 5.5 and serosal pH 7.4) and was completely inhibited by DCCD (10(-5) M). The basolateral membranes of the principal cells in frog skin epithelium were found to be spontaneously permeable to H+ and passive electrogenic H+ transport across this membrane was not affected by oxytocin. Lowering the pH of the basolateral bathing solution (pHb) produced an intracellular acidification and membrane depolarization (and an increase in conductance when the normal dominant K+ conductance of this membrane was abolished by Ba2+ 1 mM). These effects of low pHb were blocked by micromolar concentrations of heavy metals (Zn2+, Ni2+, Co2+, Cd2+, and Hg2+). Lowering pHb in the presence of oxytocin (50 mU/ml) produced a transepithelial current (3 microA.cm-2 at pHb 5.5) which was blocked by 100 microM of Hg2+, Zn2+, or Ni2+ at the basolateral side, and by DCCD (10(-5) M) or Hg2+ (100 microM) from the apical side. The net hydroosmotic water flux (JH2O) induced by oxytocin in frog bladder sacs was blocked by inhibitors of H(+)-adenosine triphosphatase (ATPase). Diethylstilbestrol (DES 10(-5) M), oligomycin (10(-8) M), and DCCD (10(-5) M) prevented JH2O when present in the lumen. These effects cannot be attributed to inhibition of metabolism since cyanide (10(-4) M), or 2-deoxyglucose (10(-3) M) had no effect on JH2O.(ABSTRACT TRUNCATED AT 400 WORDS)
J Gen Physiol 1991 Apr
PMID:Common channels for water and protons at apical and basolateral cell membranes of frog skin and urinary bladder epithelia. Effects of oxytocin, heavy metals, and inhibitors of H(+)-adenosine triphosphatase. 164 38

1. Jatrophone (JAT), a diterpene isolated from the plant Jatropha elliptica (1-300 microM), caused a concentration-dependent relaxation effect against acetylcholine (Ach)-oxytocin (Ot)- and KCl-induced uterine sustained contraction. The relative potency order was: Ach greater than Ot greater than KCl. 2. The relaxant effect of JAT was not modified by phorbol ester, forskolin, MIX, TMB-8 and W-7. The increase concentration of calcium (0.2-2 mM) in the medium did not reverse the inhibitory effect caused by JAT. 3. Pre-incubation of the preparations with JAT (16-32 microM) for 20 min, caused a concentration-dependent inhibition of KCl-induced contractile response. At 30 microM, JAT inhibited in an apparently non-competitive manner CaCl2-induced contraction in K+-depolarized preparations. High concentrations of JAT (100 microM) also caused a time-dependent relaxation in CaCl2-induced sustained uterine contraction (T1/2 = approx. 15 min). 4. JAT (30 microM) inhibited the dihydropyridine calcium channel agonist Bay K 8644-induced uterine contraction in an apparently non-competitive fashion, while verapamil (0.1 microM) caused an rightward displacement of Bay K 8644 contraction and marked inhibition of the maximal response.
Gen Pharmacol 1990
PMID:Evidence for the mechanism of the inhibitory action of jatrophone in the isolated rat uterine muscle. 168 18

1. The effects of phenidone (P, 10(-4)-10(-3) M), sodium diclofenac (D, 10(-5)-10(-4) M) and ethacrynic acid (E, 10(-5)-10(-4) M), proposed as inhibitors of eicosanoid synthesis, on the contractions of rat uterus induced by several agonists have been studied. 2. P, D and E inhibit the motility induced by oxytocin (4 mU/ml) (IC50: 4.62 x 10(-4), 2.55 x 10(-4) and 2.98 x 10(-5) M, respectively). 3. P (10(-3) M), D (10(-4) M) and E (10(-4) M) also inhibit the contraction induced by methacholine (10(-5) M), prostaglandin F2a (10(-6) M) and CaCl2 (6 mM), and relaxed, in a dose-dependent way, the tonic component of contraction to KCl (60 mM) (IC50: 5.81 x 10(-4), 6.67 x 10(-5) and 7.55 x 10(-5) M, respectively). 4. The CaCl2 (0.1-10 mM) reverted the relaxation of KCl contraction produced by P, but not by D or E. None of the inhibitions on CaCl2 (6 mM) are reverted by Bay K 8644. 5. D and E also relaxed the tonic contraction to vanadate (10(-4) M) in uterus incubated in calcium free solution P, enhances the vanadate-induced contractions.
Gen Pharmacol 1991
PMID:Mechanisms involved in the effects of phenidone, diclofenac and ethacrynic acid in rat uterus in vitro. 171 10

1. The effects of 5 pregnane compounds isolated from the rhizomes of Mandevilla illustris were examined against bradykinin (BK), Lysyl-bradykinin (L-BK), acetylcholine (ACh) and oxytocin (Ot)-induced contractions in the isolated uteri of the rat. 2. Compounds MI 15 and MI 18 (5-40 micrograms/ml) caused a parallel and concentration-dependent rightward displacement of BK and L-BK concentration-response curves. Compound MI 21 (2.5-10 micrograms/ml) also produced a concentration-dependent displacement to the right of the BK concentration-response curve, but reduced its maximal response. Schild analysis of these data were linear (r close to 1) and furnished the following PA2 values (as G/ml): 6.0, 5.1 and 5.9, respectively. However, the slopes were significantly higher than unity. Compounds MI 25 and MI 27 (10-40 micrograms/ml) caused little or even no effect against BK and ACh responses. 3. In addition, compounds MI 18 and MI 21 (10-40 micrograms/ml) also antagonized in a concentration-dependent manner L-BK concentration-response curves. Schild plot were linear (r close to 1) and yielded the nominal pA2 values (as G/ml) of 5.0 and 5.8, respectively, but the slopes were significantly different from one. 4. Like the results obtained previously with the crude extract from M. illustris, the purified compounds from the rhizome of this plant were not selective towards kinin action since at the same range concentrations they markedly interfered with both the sensitivities and the maximal responses caused by ACh and Ot in this preparation.
Gen Pharmacol 1991
PMID:Action of pregnane compounds from Mandevilla illustris against contractions induced by kinins and other oxytocics in the rat isolated uterus. 181 Aug 5

1. The modification of the contraction of the rat testicular capsule to oxytocin (OT) by vanadate (0.7, 7 and 70 microM), ouabain (0.1 mM), and amiloride (10 microM to 1 mM) have been studied. 2. OT (1 nM-6 microM) and vanadate (10 microM-3 mM) induced contraction of the rat testicular capsule in a dose-dependent way (ED50: 188 +/- 66 nM and 82.8 +/- 7.4 microM, respectively). 3. Vanadate (0.7, 7 and 70 microM) and ouabain (0.1 mM) increases the contractile effect of OT (50 and 200 nM). 4. Amiloride (10 microM-1 mM) inhibit, in a dose-dependent way, the OT-contraction. 5. Amiloride (10 microM or 50 microM) block the ouabain but not the vanadate potentiation to OT.
Gen Pharmacol 1991
PMID:Effects of vanadate, ouabain and amiloride on the contraction of the rat testicular capsule to oxytocin. 193 5


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