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)

Luteinizing hormone is the major regulator of Leydig cell differentiation and steroidogenic function. A number of hormones produced by the Leydig cell (e.g. estrogen, angiotensin, CRF, vasopressin) and the tubular compartment (inhibin, TGF beta), can influence both acute and long-term actions of LH. Conversely, hormones produced in the Leydig cells modulate tubular function (e.g. androgen, beta-endorphin, oxytocin). The LH stimulatory event can be negatively influenced by the action of angiotensin II through the guanyl nucleotide inhibitory unit of adenylate cyclase. We have recently discovered an action of corticotrophin releasing hormone through specific high-affinity low-capacity receptors in the Leydig cells which involves a pertussis toxin insensitive guanyl nucleotide regulatory unit with interaction between signalling pathways and resulting inhibition of LH induced cAMP generation and consequently of steroidogenesis. In contrast to other tissues the CRF receptor in the Leydig cells did not couple to Gs. CRF action is exerted through direct or indirect action of protein kinase C, at the level of the catalytic subunit of adenylate cyclase. Physiological increases in endogenous LH cause positive regulation of membrane receptors and steroidogenesis, while major elevations in circulating gonadotropin can induce down-regulation of LH receptors and desensitization of steroid responses in the adult cell. Gonadotropin-induced desensitization in adult rat tests include an estrogen mediated steroidogenic lesion of the microsomal enzymes 17 alpha-hydroxylase/17,20-desmolase. For further understanding of the regulation of this key enzyme of the androgen pathway the rat P450(17) alpha cDNA was cloned and sequenced. This cDNA expressed in COS-1 cells 17 alpha-hydroxylase/17,20-desmolase activities. From the deduced amino acid sequence, two transmembrane regions were identified, a signal peptide for insertion in the ER, and a 2nd transmembrane region separated from the first by 122 amino acids. The carboxy terminal non-transmembrane region possesses 4 hydrophobic clefts, of which cleft II would contain the putative steroid binding site for both hydroxylase and lyase activities. The rat cDNA was employed to evaluate the hormonal regulation of mRNA levels in adult and fetal Leydig cells. Low dose hCG treatment caused an early increase in mRNA levels followed by a return to control values at later times, while with higher desensitizing doses the initial increase in mRNA was followed by a marked reduction in mRNA at 24 h and a small recovery at 48 h. Fetal rat Leydig cells treated with E2 showed a 70% decrease in P450 mRNA levels, and testosterone production closely followed the changes in mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:LH action in the Leydig cell: modulation by angiotensin II and corticotropin releasing hormone, and regulation of P450(17) alpha mRNA. 269 45

Arginine vasopressin (AVP) is a potent neuroactive and vasoactive nonapeptide encoded in and processed from a precursor, preproarginine vasopressin-neuro-physin II (preproAVP-NPII). To study the physiologic consequences of a genetic model of chronic hypervasopressinemia transgenic mice were produced by introduction of a mouse metallothionein-rat-ppAVP-NPII fusion gene into the germ line of mice. Three stable transgenic pedigrees were analyzed through several generations. Levels of immunoreactive AVP and neurophysin (NP) in sera, livers, kidneys, intestines, pancreas, and brains were markedly elevated. Chromatographic analyses showed sera levels of approximately 500 pg/ml (normal 0-20 pg/ml) of authentic AVP non-apeptide and serum osmolalities were elevated, 315.4 +/- 1.4 mosm/liter (control, 307.3 +/- 1.1), consistent with a state of mild nephrogenic diabetes insipidus. Brain levels of immunoreactive AVP in transgenic mice were 3-4-fold elevated 145 +/- 15 ng/g versus 31 +/- 7 (controls). Although immunoreactive AVP in livers and intestines, and to some extent kidneys, consisted predominantly of unprocessed precursors, in brain and pancreas greater than 90% of AVP consisted of processed bioactive nonapeptide, as determined by chromatography and measurements of cAMP-generation in LLC-PK1 cells. Immunocytochemistry localized immunoreactive AVP to the exocrine pancreas and to the magnacellular neurons (SON and PVN) of the hypothalamus. Expression of the fusion gene in the hypothalamus was further demonstrated by Northern analyses of fusion gene specific transcripts and in situ histohybridization. Although the fusion gene contained only 35 base pairs of 5'-flanking DNA of the ppAVP-NPII gene, a tentative neuronal cell-specific expression element, -17GCCCAG-CC-10 resides in this sequence and may confer neuron-specific expression to the fusion gene.
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PMID:Metallothionein-vasopressin fusion gene expression in transgenic mice. Nephrogenic diabetes insipidus and brain transcripts localized to magnocellular neurons. 280 95

Increasing concentrations of fendiline inhibit various types of muscle activation (KCl, oxytocin and electrical stimulation), as well as spontaneous rhythmic activity of the isolated uterus of the rat. Contrary to verapamil and nifedipine, fendiline in micromolar concentrations (from 1.5 to 15.5 mumol) affects various types of muscle activation almost to the same degree. Fendiline probably influences a common pathway in calcium metabolism in all types of muscle activation. The relaxant effect of fendiline does not depend on cAMP, being even associated with a significant decrease of the level of this nucleotide during electrical stimulation of the isolated uterus of the rat. Fendiline may have its place in the therapy of premature delivery and abortion, particularly because it exhibits lower selectivity in relation to the type of activation of the smooth muscle. Fendiline induces a stronger inhibition of the tonic than of the phasic component of contraction produced by oxytocin and KCl. Fendiline is more active against the oxytocin-induced contraction, probably due to an additional action on the fast Na+ channels. These findings indicate that KCl and oxytocin act through different calcium channels (voltage and receptor calcium channels). Our experiments in which fendiline inhibited more strongly the tonic than the phasic component of KCl-produced contraction also confirm the hypothesis on the existence of voltage calcium channels (or subtypes of one voltage calcium channel) in the isolated uterus of the rat. By adding calcium to the medium, almost all types of muscle activation are established, after the inhibitory action of fendiline, except its depressive action on the electrical stimulation of the isolated rat uterus. Calcium most effectively antagonizes the inhibitory effect of fendiline on spontaneous rhythmic activity. The finding that certain types of activation, after the inhibitory action of fendiline, occur to a different degree by addition of calcium to the medium, are also indirect confirmation of the existence of different calcium channels. Halothane, in a concentration of 1 vol %, did not change the relaxant action of fendiline during electrical stimulation and during spontaneous rhythmic activity.
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PMID:The effect of fendiline on cAMP metabolism and activity of the isolated uterus of the rat. 282 Mar 25

This study reports the presence in AtT-20 corticotrophs of high affinity-low capacity receptors for arginine-vasopressin (AVP), whose binding capacity was considerably enhanced by the divalent metal ion nickel. These binding sites, when analyzed in the presence of nickel, showed high affinity for AVP, vasotocin and oxytocin, but recognized to a lesser extent the V2-agonist 1-deamino-AVP, as well as V1-antagonists. Surprisingly, AVP failed to alter secretion of proopiomelanocortin (POMC)-derived peptides from the cells or corticotropin-releasing factor (CRF)-induced cAMP synthesis, as reported in normal corticotrophs. Exposure of cells to CRF elicited an increase in mRNAPOMC levels, while, in contrast, AVP was without significant effect. It thus appears that in AtT-20 tumor cells, the AVP receptors are not coupled to either the biochemical or biological cellular response.
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PMID:Evidence that AVP receptors in AtT-20 corticotrophs are not coupled to secretion of POMC-derived peptides. 282 11

Vasopressin and oxytocin immunoreactivity (AVP-IR, OT-IR) have been detected in the trigeminal and dorsal root ganglia (TG, DRG) of the rat. We have investigated whether AVP or OT have any neurotransmitter role in these tissues by measuring the effects of the peptides on levels of intracellular second messengers. AVP and OT at concentrations up to 3 x 10(-6) M have no effect on the accumulation of cAMP. However, in tissue prelabelled with 3H-inositol, and in the presence of 10 mM Li+, AVP and OT cause an increase in the accumulation of inositol phosphates (IP), in a dose-dependent manner. AVP causes a maximum stimulation of 1.7 fold of control in TG, (p less than 0.01) and of 2.5 fold in DRG (p less than 0.01) at a concentration of 3 x 10(-7) M. OT causes a maximum stimulation of 1.3 fold of control in TG, (p less than 0.01), and of 1.75 fold of control in DRG, at a concentration of 3 x 10(-6) M. The stimulation of IP turnover by AVP in both tissues is inhibited by the specific V1-antagonist, (CH2)5Tyr(Me)AVP, at a concentration of 2 x 10(-5) M. The V2-agonist, DDAVP, has no effect on IP accumulation in either tissue at concentrations up to 3 x 10(-6) M. The response to exogenous AVP is still present in ganglia incubated in media without added CaCl2. We conclude that the rat TG and DRG contain receptors for AVP, and that these receptors have characteristics associated with the V1 subtype.
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PMID:Vasopressin-induced turnover of phosphatidylinositol in the sensory nervous system of the rat. 282 10

Control of ACTH secretion in the pituitary in the absence of target cells for CRF, the most potent ACTH secretagogue, was studied in dissociated bovine anterior pituitary cells treated with a potent selective cytotoxin. The cytotoxin is a conjugate of the CRF analog [Nle21,38, Arg36]rat (r) CRF and the plant toxin gelonin. Dissociated bovine anterior pituitary cells were pretreated with vehicle, 2 nM ovine CRF, 2 nM cytotoxic conjugate, or unconjugated [Nle21,38,Arg36]rCRF and gelonin in amounts equivalent to that of 2 nM cytotoxic conjugate for 12 h, then extensively washed and cultured for 3 days before acute secretion experiments. Unstimulated ACTH secretion was similar in all groups. ACTH secretion in response to CRF was attenuated by pretreatment with the cytotoxic conjugate; CRF (2.5 nM)-stimulated secretion was 7.0, 6.3, and 2.8 times the unstimulated rate in cells pretreated with vehicle, 2 nM CRF, or 2 nM cytotoxic conjugate, respectively. Likewise, the ACTH secretory response to a cAMP analog was attenuated by pretreatment with the conjugate; 8-bromo-cAMP (10 mM)-stimulated secretion was 6.8, 7.1, and 3.3 times the unstimulated rate in cells pretreated with vehicle, CRF, or conjugate, respectively. In contrast, the ACTH responses to vasopressin (VP) or oxytocin (OR) remained intact. VP stimulated the ACTH secretion rate by 4.2, 4.0, and 3.5 times, respectively, in the three groups. OT stimulated the ACTH secretion rate by 2.7, 2.6, and 2.3 times in the three groups. Pretreatment with the conjugate attenuated the response to CRF and VP in combination by the same amount as it attenuated the response to CRF alone. The ACTH secretory responses in cells pretreated with unconjugated [Nle21,38,Arg36]rCRF and gelonin were not different from responses in cells pretreated with vehicle. These results suggest that there is a separate mechanism or cell type for OT- and VP-stimulated ACTH secretion distinct from that responsible for the action of CRF on pituitary cells.
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PMID:Dissociation of the adrenocorticotropin secretory responses to corticotropin-releasing factor (CRF) and vasopressin or oxytocin by using a specific cytotoxic analog of CRF. 283 Oct 39

We incubated toad urinary bladders with Na+-free, isotonic K+ solutions on the apical side and increased the cationic conductance of the apical membrane with nystatin (150 U/ml). Under these conditions, the short-circuit current is mostly carried by K+ flowing from mucosa to serosa. Impedance measurements showed that in nystatin-treated preparations, the electrical behavior of the tissue is dominated by the basolateral membrane properties. Oxytocin (0.1 U/ml) produced an increase of the current and the conductance of the basolateral membrane. Both the resting and the oxytocin-stimulated current were rapidly and reversibly blocked by serosal Ba2+. Addition of the adenosine 3',5'-cyclic monophosphate (cAMP) analogue [8-(4-chloropheylthio)-cAMP] to the basolateral solution mimicked the effects of oxytocin. These results show that oxytocin and cAMP stimulate a potassium conductance in the basolateral membrane and that the stimulation is not related to an increase in sodium entry through the apical membrane. Addition of ouabain (10(-3) M) to the serosal solution did not modify the stimulation by oxytocin, indicating that the activated pathway is not linked to the rate of turnover of the Na+ pump.
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PMID:Activation of K+ conductance in basolateral membrane of toad urinary bladder by oxytocin and cAMP. 283 95

The effects of calcitonin (CT) on the water transfer in the toad (Bufo arenarum) urinary bladder, an epithelial barrier commonly employed as a model of the mammalian nephron, were studied. The net transmembrane water flux was measured at minute intervals, while the endogenous adenosine 3',5'-cyclic monophosphate (cAMP) levels were determined in isolated epithelial cells. It was observed that 1) CT, up to 10(-6) M, did not have any effect on water permeability. 2) Preincubation with CT, between 10(-7) and 10(-8) M, inhibited the hydrosmotic response to a supramaximal dose of oxytocin (OXT; 2 x 10(-8) M), used here as an antidiuretic hormone (ADH) analogue. This inhibition was reversible and concentration related. Nevertheless, although the magnitude of the response was reduced, its time course of evolution did not change. 3) When CT was added on the previously developed response to OXT, inhibition was also dose dependent with a time course not distinguishable from hormonal washout. 4) CT, up to 10(-6) M, did not modify the hydrosmotic response to 8-bromo cAMP, a potent analogue of the ADH second messenger. 5) CT and OXT increased the intracellular cAMP levels, but both effects were not cumulative. The increase induced by CT plus OXT was significantly lower than the one elicited by OXT alone. It is concluded that CT is a competitive inhibitor to the hydrosmotic effect of OXT in toad urinary bladder. Its action must be located prior to cAMP formation.
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PMID:Calcitonin is a competitive inhibitor of the hydrosmotic effect of oxytocin in toad bladder. 284 37

The effects of oxytocin and cAMP on the electrogenic Na+-transport in the short-circuited epithelium of the frog colon (Rana esculenta, Rana temporaria) were investigated. Oxytocin (100 mU.ml-1) elevated the short-circuit current (Isc) transiently by 70% whereas cAMP (1 mmol.l-1) elicited a comparable sustained response. The mechanism of the natriferic action of cAMP was studied by analysing current fluctuations through apical Na+-channels induced by amiloride or CDPC (6-chloro-3,5-diaminopyrazine-2-carboxamid). The noise data were used to calculate Na+-channel density (M) and single apical Na+-current (iNa). iNa-Values obtained with amiloride and CDPC were 1.0 +/- 0.1 pA (n = 5) and 1.1 +/- 0.2 pA (n = 6) respectively and unaffected by cAMP. On the other hand, cAMP caused a significant increase in M from 0.23 +/- 0.08 micron-2 (n = 5) to 0.49 +/- 0.17 micron-2 (n = 5) in the amiloride experiments. In our studies with CDPC we obtained smaller values for M in control (0.12 +/- 0.04 micron-2; n = 6) as well as during cAMP treatment (0.19 +/- 0.06 micron-2; n = 6). However, the cAMP-induced increase in M was also significant. We conclude that cAMP stimulates Na+-transport across the frog colon by activating "silent" apical Na+-channels. Thus, the mechanism of regulation of colonic Na-transport in frogs differs considerably from that in other vertebrates as mammals and birds.
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PMID:Noise analysis of cAMP-stimulated Na current in frog colon. 285 May 32

The effects of fluphenazine, a phenothiazine calmodulin inhibitor, on the osmotic water flow (Posm) across isolated skins of Bufo arenarum toads were tested. Fluphenazine inhibited the increase in Posm induced by agents known to act through the cyclic AMP system (oxytocin, db-cAMP, theophylline, KCl and isoproterenol). The inhibitory effect was faster and more intense when the drug was present in the epidermal bath, and persisted after rinsing the preparation for 100 min. Our results indicate that phenothiazine's action may be primarily exerted at a site distal to cyclic AMP generation.
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PMID:Inhibition of stimulated osmotic water flow by fluphenazine, a calmodulin inhibitor, in the isolated toad skin. 286 Oct 50


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