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)

1. Glibenclamide, a blocker of ATP-sensitive potassium channels, has been shown to antagonize relaxin as a uterine relaxant in the rat in vivo but not in vitro. The aim, therefore, was to investigate whether the discrepancy between the two studies was a consequence of differences in (1) muscle layers, (2) hormonal conditions or (3) spasmogens utilized. Relaxin was compared with salbutamol and levcromakalim. 2. Relaxin was of similar potency as a uterine relaxant against oxytocin (0.2 mM)-induced spasm with tension measured in the circular or longitudinal muscle layers. Glibenclamide (10 microM) did not antagonize relaxin or salbutamol in these preparations but greatly antagonized levcromakalim (91-fold). Relaxin was a relaxant of tension activated by transmural electrical stimulation in uteri from rats that had been ovariectomized, although the maximal effect was only 30 +/- 15%, and in uteri from rats that had been treated with 17 beta-estradiol benzoate. Glibenclamide was not an antagonist of relaxin in the latter preparation but did antagonize levcromakalim (118-fold). Relaxin also inhibited spontaneous phasic tension development in uteri from ovariectomized rats but again was not antagonized by glibenclamide. 3. Because relaxin was not antagonized by glibenclamide under any of these various conditions, it would appear that the in vivo-in vitro discrepancy in the antagonism of relaxin by glibenclamide is not attributable to the effects of different muscle layers, hormonal conditions or spasmogens. It may be that the mechanism of action of relaxin or glibenclamide or both differs between in vivo and in vitro preparations.
Gen Pharmacol 1997 Nov
PMID:Relaxin as a relaxant of the isolated rat uterus: comparison with its mechanism of action in vivo. 934 34

1. Modulatory effects of APGW-amide (Ala-Pro-Gly-Trp-NH2), proposed as an inhibitory neurotransmitter of Achatina neurons, perfused at 3 x 10(-6) M on the currents induced by neuroactive peptides, ejected by brief pressure, were examined by using Achatina giant neuron types, v-RCDN (ventral-right cerebral distinct neuron) and PON (periodically oscillating neuron), under voltage clamp. 2. Outward current (Iout) caused by FMRFamide (Phe-Met-Arg-Phe-NH2) on v-RCDN, which was probably K+ dependent, was inhibited with membrane conductance (g) increase by APGW-amide. From the dose (pressure duration)-response curves of FMRFamide and a Lineweaver-Burk plot of these data, the inhibition caused by APGW-amide was mainly in an uncompetitive manner. 3. Iout caused by APGW-amide on v-RCDN, which was probably K+ dependent, was inhibited with g increase by APGW-amide. The inhibition caused by APGW-amide was partly in a competitive manner and partly in a noncompetitive manner. 4. Iout caused by [Ser2]-Mytilus inhibitory peptide, [Ser2]-MIP (Gly-Ser-Pro-Met-Phe-Val-NH2) on v-RCDN, which was probably K+ dependent, was inhibited with g increase by APGW-amide. Because the modulation of this current was not so marked, a dose-response study of this compound was not carried out. Iin induced by oxytocin on PON was not affected by APGW-amide. 5. From the dose-response curves of APGW-amide, perfused consecutively, the inhibitory effects of APGW-amide on the Iout caused by APGW-amide were stronger than those on the Iout caused by FMRFamide. 6. The inhibition of the APGW-amide-induced Iout on v-RCDN by APGW-amide was partly due to the competition in the receptor sites and partly to the g increase. The inhibition by APGW-amide on the Iout induced by FMRFamide and [Ser2]-MIP would be partly due to the g increase. In addition, we consider that APGW-amide affects intracellular signal transduction systems or ionic channels, thus modulating these currents. 7. The currents modulated by APGW-amide were different from those modulated by achatin-1, another Achatina endogenous neuroexcitatory peptide. We consider that the mechanisms underlying the modulatory effects of APGW-amide are different from those of achatin-I.
Gen Pharmacol 1997 Oct
PMID:Modulation by APGW-amide, an Achatina endogenous inhibitory tetrapeptide, of currents induced by neuroactive compounds on Achatina neurons: peptides. 935 98

Arginine vasotocin (AVT) is present in the neurohypophysis of all nonmammalian vertebrates and it appears to be the antecedent of the neurohypophysial nonapeptide hormones. Relatively little is known about AVT receptors in lower vertebrates, especially fish, and the present study was designed to examine AVT receptor interactions in trout vascular and nonvascular smooth muscle in vitro. AVT produced dose-dependent contraction of isolated rings from celiacomesenteric, coronary, and efferent branchial arteries, ventral aorta, anterior cardinal vein, and strips of ductus Cuvier. The greatest efficacy (magnitude of contraction per unit tissue weight) and sensitivity (effective concentration for half-maximal response, EC50) to AVT was found in the efferent bronchial artery (EBA) and its receptors were characterized further. Other neurohypophysial peptides, including arginine vasopressin (AVP), lysine vasopressin (LVP), isotocin (IST), and oxytocin (OXY), contracted EBA with an efficacy order of (most to least) AVT = AVP = OXY > LVP > IST and a sensitivity order of AVT > OXY >/= AVP > IST > LVP. Neither Desmopressin, an AVP V2-receptor agonist, nor the AVP ring fragment, AVP4-9, contracted EBA nor did they inhibit AVT contraction. Pretreatment of EBA rings with the selective AVP V1-receptor antagonists (deamino-Pen1, O-Me-Tyr2, Arg8-vasopressin and deamino-Pen1, Val4, Arg8-vasopressin), the selective V2-receptor antagonist (adamantaneacetyl1, O-Et-D-Tyr0, Val4, aminobutyryl6, Arg8,9-vasopressin), or the combined V1-oxytocin receptor antagonist (d(CH2)5[Tyr(Me)2, Orn8-AVT]) competitively inhibited AVT contractions without affecting AVT efficacy. Receptor affinity constants (pA2) determined by Schild analysis were in the range of 6.8-7.3, with slightly higher constants for the AVP V1-/oxytocin receptor antagonists than for the selective V2-receptor antagonist. Endothelium removal had no effect on EBA sensitivity to AVT. EBA rings were an order of magnitude more sensitive to AVT than nonvascular gastrointestinal and urinary bladder smooth muscle rings or strips. However, AVT (10(-7) M) was as efficacious as acetylcholine (10(-5) M) in gastrointestinal, gallbladder, and urinary bladder smooth muscle. It is concluded that trout EBA possess an AVT smooth muscle receptor that shares a similar pharmacological profile with the mammalian vascular AVP V1a-receptor and the OXY-receptor, but it is distinct from the previously reported gill epithelial cell receptor.
Gen Comp Endocrinol 1999 Apr
PMID:Pharmacological characterization of arginine vasotocin vascular smooth muscle receptors in the trout (Oncorhynchus mykiss) in vitro. 1009 57

Sequences coding for pro-vasotocin and pro-isotocin have been identified by screening a flounder (Platichthys flesus) hypothalamic cDNA library. The 1074-bp proVT and 727-bp proIT sequences contain a signal peptide and hormone, connected to a neurophysin by a Gly-Lys-Arg sequence. Both sequences also have an elongated carboxyl-terminal with a leucine-rich core resembling copeptin but lacking the amino terminal Arg residue. The levels of pro-vasotocin and pro-isotocin mRNA in the hypothalamus were measured concomitantly with pituitary AVT content and plasma AVT concentration following acute transfer of fish between freshwater and seawater. Three days after transfer from seawater to freshwater there appears to be a down regulation of the AVT hormone system with a fall in hypothalamic pro-vasotocin mRNA levels, an increase in pituitary AVT content, and a fall in plasma levels, but these changes did not achieve statistical significance compared to controls. No change in the AVT system was detected 3 days following the transfer of fish from freshwater to seawater. Hypothalamic isotocin mRNA levels did not change following hypo- or hyperosmotic challenge.
Gen Comp Endocrinol 2000 Jul
PMID:Cloning of pro-vasotocin and pro-isotocin cDNAs from the flounder Platichthys flesus; levels of hypothalamic mRNA following acute osmotic challenge. 1088 52

The oxytocin (OT)-like peptide of most Australian marsupials is mesotocin (MT), which differs from OT by substitution of isoleucine for leucine at position 8. To date, the only information on the evolution of the OT peptide in marsupials is based on the sequence of the 9-amino acid peptide itself. The main objective of this study was to obtain the nucleotide and derived amino acid sequences of a marsupial MT precursor for comparison with known OT and MT precursors of eutherians and nonmammalian vertebrates. The structural organization and sequence of the MT gene and its specific transcript were established in a macropodid marsupial, the tammar wallaby, using PCR strategies with a combination of genomic DNA and reverse-transcribed hypothalamic RNA. A consensus genomic sequence of 1221 bp was produced which, by comparison with the expressed cDNA sequence, included two intron sequences of 480 and 188 bp. The tammar MT precursor molecule consists of a 32-amino acid signal peptide, followed by the MT-encoding region and the Gly-Lys-Arg carboxy-terminal cleavage and amidation signal which separates the nonapeptide from the 92-amino acid neurophysin. At the amino acid level, the MT precursor is more similar to eutherian OT precursors than to nonmammalian MT, isotocin, or vasotocin precursors. Northern analysis demonstrated a single transcript of approximately 0.6 kB in the hypothalamus. Mesotocin mRNA is also present in several tissues of the reproductive tract, including the corpus luteum, follicle, uterus, and placenta. Within the ovary, MT transcripts are localized predominantly in the granulosa cells of antral follicles with some positive hybridization signals in cells of the theca interna. This pattern of MT gene expression in marsupials is very similar to that of OT in eutherians and suggests a conserved physiology in the mammalian ovary.
Gen Comp Endocrinol 2000 May
PMID:Mammalian mesotocin: cDNA sequence and expression of an oxytocin-like gene in a macropodid marsupial, the tammar wallaby. 1089 May 61

This article provides a review of the past and current literature on the neurobiology of sexual function. The influence of endocrine, neurotransmitter, and central nervous system influences on male and female sexual function are discussed for sexual desire, arousal, and orgasm or ejaculation stages of sexual responding. Endocrine factors reviewed include the following: androgens, estrogens, progesterone, prolactin, oxytocin, cortisol, and pheromones. Neurotransmitters and neuropeptides discussed include nitric oxide, serotonin, dopamine, epinephrine, norepinephrine, opioids, acetylcholine, histamine, and gamma-aminobutyric acid. Central nervous system influences on sexual function are discussed briefly with reference to brainstem regions, the hypothalamus, and the forebrain.
Arch Gen Psychiatry 2000 Nov
PMID:The neurobiology of sexual function. 1198 56

A sequence coding for an arginine vasotocin (AVT) receptor has been identified by the screening of a hepatic cDNA library from the teleost Platichthys flesus. The 2701-bp receptor sequence is predicted to yield a 384-amino acid peptide, analysis of which indicates a seven-transmembrane spanning sequence typical of G-protein-coupled receptors with the N terminus on the outer surface of the cell membrane. Sequence analysis showed this sequence to have a high homology with the Catostomus commersoni AVT receptor (76%) and mammalian vasopressin V(1)-type receptor (62%), but only 55% homology with the C. commersoni isotocin receptor. A two-electrode voltage clamp was used to characterize the receptor expressed in Xenopus laevis oocytes. AVT induced an inward current which was dose dependent over the range 16.7 fmol to 5 pmol; isotocin was without effect over the same dose range. The mammalian vasopressin V(1)-type receptor agonist ([Phe(2), Orn(8)] oxytocin)() induced an inward current but was less potent than AVT, whereas the mammalian vasopressin V(2)-type receptor agonist ([Deamino(1), Val(4), D-Arg(8)] AVP) was without effect. Injection of oocytes with heparin or BAPTA suppressed the response to AVT, indicating receptor linkage to the phospholipase C-phosphatidylinositol pathway. Northern analysis demonstrated the presence of this AVT receptor mRNA in the brain, kidney, and gill of flounder.
Gen Comp Endocrinol 2001 Jun
PMID:Cloning and characterization of an arginine vasotocin receptor from the euryhaline flounder Platichthys flesus. 1135 43

In most amphibians, [Arg(8)] vasotocin (VT) has an antidiuretic effect that is coupled to the activation of adenylate cyclase. In contrast, mesotocin (MT) has a diuretic effect and acts via the inositol phosphate/calcium signaling pathway in amphibians. To further clarify the mechanisms of VT and MT activation, we report the molecular cloning of a VT receptor (VTR) and a MT receptor (MTR) from the Japanese tree frog, Hyla japonica. Tree frog VTR or MTR cDNA encoded 363 or 389 amino acids, and their amino acid sequences revealed close similarity to the mammalian vasopressin V(2) (51-52% identity) or toad MT (94% identity) receptors, respectively. Using CHO-K1 cells transfected with tree frog VTR, we observed elevated concentrations of intracellular cAMP following exposure of the cells to VT or other neurohypophysial hormones, whereas the cells transfected with MTR did not exhibit altered cAMP concentrations. The cells transfected with VTR exhibited the following efficiency for cAMP accumulation: VT = hydrin 1 > or = vasopressin > or = hydrin 2 > MT = oxytocin > isotocin. VTR or MTR mRNA exhibits a single 2.2- or 5.5-kb transcription band, respectively, and both are expressed in various tissues. VTR mRNA is clearly expressed in brain, heart, kidney, pelvic patch of skin, and urinary bladder, whereas brain, fat body, heart, kidney, and urinary bladder express MTR mRNA. Specifically, VTR mRNA in the pelvic patch or MTR mRNA in the dorsal skin is present at elevated levels in the skin. Characteristic distribution of VTR and MTR on osmoregulating organs indicates the ligands for these receptors would mediate a variety of functions. Further, the distribution of VTR in the skin would make the regional difference on cutaneous water absorption in response to VT in the Japanese tree frog.
Gen Comp Endocrinol 2003 Jul
PMID:Molecular cloning of an anuran V(2) type [Arg(8)] vasotocin receptor and mesotocin receptor: functional characterization and tissue expression in the Japanese tree frog (Hyla japonica). 1284 72

Studies were made of the active ion transport by the isolated urinary bladder of the European toad, Bufo bufo, and the large American toad, Bufo marinus. The urinary bladder of the toad is a thin membrane consisting of a single layer of mucosal cells supported on a small amount of connective tissue. The bladder exhibits a characteristic transmembrane potential with the serosal surface electrically positive to the mucosal surface. Active sodium transport was demonstrated by the isolated bladder under both aerobic and anaerobic conditions. Aerobically the mean net sodium flux across the bladder wall measured with radioactive isotopes, Na(24) and Na(22), just equalled the simultaneous short-circuit current in 42 periods each of 1 hour's duration. The electrical phenomenon exhibited by the isolated membrane was thus quantitatively accounted for solely by active transport of sodium. Anaerobically the mean net sodium flux was found to be slightly less than the short-circuit current in 21 periods of observation. The cause of this discrepancy is not known. The short-circuit current of the isolated toad bladder was regularly stimulated with pure oxytocin and vasopressin when applied to the serosal surface under aerobic and anaerobic conditions. Adrenaline failed to stimulate the short-circuit current of the toad bladder.
J Gen Physiol 1958 Mar 20
PMID:Active sodium transport by the isolated toad bladder. 1351 2

The response of the isolated amphibian urinary bladder to thirty-four structural analogs of arginine vasotocin was determined in an effort to define the physiological significance of specific structural groups on the hormone molecule. All but one of the analogs tested possessed full intrinsic activity in this system but varied greatly in their affinity for the receptor site. An analysis of the effect of changes in hydrogen ion concentration upon the response of the bladder to oxytocin was performed in order to determine the number and nature of the ionizable groups involved in hormone receptor interaction. Two ionizable groups with apparent pK's of 7.1 and 7.75 were found to be important in determining the magnitude of the hormonal response. On the basis of the results it was postulated that hormone-receptor interaction can be considered a two-step process: (a) The binding or attachment of hormone to receptor site through ionic, hydrogen, and hydrophobic bonds and (b) a disulfide interchange reaction between hormonal disulfide and receptor sulfhydryl. The latter step is considered to be the reaction which initiates the chain of events leading to the observed change in permeability.
J Gen Physiol 1963 Jul
PMID:STRUCTURAL REQUIREMENTS FOR THE ACTION OF NEUROHYPOPHYSEAL HORMONES UPON THE ISOLATED AMPHIBIAN URINARY BLADDER. 1404 98


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