Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the mechanism for lithium-induced inhibition of vasopressin-stimulated adensoine 3',5'-cyclic monophosphate (cAMP) production in the renal epithelial cell line LLC-PK1. In LLC-PK1 membranes lithium caused direct inhibition of hormone-stimulated adenylate cyclase activity by competing with magnesium. Fifty percent inhibition occurred at 20 mM lithium. The maximum transport activity (Vmax) but not the activation constant (Ka) for activation by vasopressin was altered. Activation by GTP and its nonhydrolyzable analogues was also inhibited by lithium. Furthermore, kinetic studies revealed that the lag phase in the activation of adenylate cyclase by 5'-guanylimi-dotriphosphate [Gpp(NH)p] was prolonged from 1 to 3 min, suggesting an effect of lithium on magnesium-dependent activation of the stimulatory GTP binding protein Gs. The function of the corresponding inhibitory GTP-binding protein Gi, as assessed by GTP inhibition of vasopressin-stimulated adenylate cyclase activity in the presence and absence of pertussis toxin pretreatment, was unaffected. Intact LLC-PK1 cells incubated in 10 mM lithium (approximate urinary concentration in lithium-treated patients) attained an intracellular lithium concentration of 17 mM, which led to a 40% reduction in cAMP formation. Magnesium loading of intact cells with the ionophore A23187 reversed the inhibitory effect of lithium. It is concluded that lithium directly inhibits the activation of vasopressin-sensitive adenylate cyclase in renal epithelia by competing with magnesium for activation of Gs. This direct effect on Gs activation accounts for the inhibitory effect of lithium on cAMP production in the intact cell.
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PMID:Mechanism of Li inhibition of vasopressin-sensitive adenylate cyclase in cultured renal epithelial cells. 246 Oct 98

Outward rectifying, cation channels were observed in the epithelial cells of the urinary bladder of the toad. Bufo marinus. As studied in isolated cells using the patch-clamp technique, the channel has an average conductance of 24 and 157 pS for pipette potentials between 0 and +60 mV and -60 to -100 mV, respectively, when the major cation in both bath and pipette solutions is K+. The conductance of the channel decreases with increasing dehydration energy of the permeant monovalent cation in the order Rb+ = K+ greater than Na+ greater than Li+. Reversal potentials near zero under biionic conditions imply that the permeabilities for all four of these cations are similar. The channel is sensitive to quinidine sulfate but not to amiloride. It shares several pharmacological and biophysical properties with an outwardly-rectifying, vasopressin-sensitive apical K+ conductive pathway described previously for the toad urinary bladder. We demonstrate, in both single-channel and whole-bladder studies, that the outward rectification is a consequence of interaction of the channel with extracellular divalent cations, particularly Ca2+, which blocks inward but not outward current. Various divalent cations impart different degrees of outward rectification to the conductive pathway. Concentrations of Mg2+ and Ca2+ required for half-maximal effect are 3 X 10(-4) and 10(-4) M, respectively. For Co2+ the values are 10(-6) M at +50 mV and a 10(-4) M at +200 mV. The mechanism of blockade by divalent cations is not established, but does not seem to involve a voltage-dependent interaction in which the blocker penetrates the transmembrane electric field. In the absence of divalent cations in the mucosal solution, the magnitudes of inward current carried by Rb+, K+, Na+ and Li+ through the apical K+ pathway at any transepithelial voltage, are in the same order as in the single-channel studies. We propose that the cation channel observed by us in isolated epithelial cells is the single-channel correlate of the vasopressin-sensitive apical K+ conductive pathway in the toad urinary bladder and is also related to the oxytocin- and divalent cation-sensitive apical conductivity observed in frog skin and urinary bladder.
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PMID:Extracellular Ca2+ controls outward rectification by apical cation channels in toad urinary bladder: patch-clamp and whole-bladder studies. 246 99

The extracellular Ca2+ dependence of agonist stimulation of vascular smooth muscle (VSM) has been investigated in rat cultured aortic smooth muscle cells (SMCs) and isolated mesenteric resistance vessels (MRVs). Agonists such as [Arg8]vasopressin (AVP), angiotensin II (Ang II), and adenosine-5'-triphosphate (ATP) stimulated 45Ca2+ entry into the SMCs that was (a) independent of the extent to which the membranes were polarized, and (b) was not inhibited by organic Ca2+ channel antagonists. Measuring the intracellular Ca2+ concentration [( Ca2+]i) after stimulation with agonists revealed a rapid increase of [Ca2+]i, which was followed by a sustained rise that was insensitive to Ca2+ antagonists. In Ca2+-free medium, only the initial peak of [Ca2+]i was still observed, but the sustained response to the agonists disappeared completely. This observation indicates that the sustained elevation seen in Ca2+-containing medium was the consequence of agonist-induced Ca2+ entry. In MRVs, a corresponding Ca2+-antagonist-insensitive, agonist (norepinephrine and AVP)-induced tonic tension was also identified. Moreover, agonists were able to induce sustained tension in the MRVs regardless of whether the membrane was normally polarized or was previously depolarized (80 mM K+) upon their administration. The agonist-stimulated 45Ca2+ entry in the SMCs could be blocked by the multivalent cations La3+, Cd2+, Mn2+, Co2+, Ni2+, and Mg2+ (in this order of potency). Depolarization-induced 45Ca2+ influx was inhibited by these cations in the same order of potency, but was significantly more sensitive to Cd2+ and significantly less sensitive to La3+ than that stimulated by agonists. Treatment with 2-nitro-4-carboxyphenyl-N,N-diphenyl-carbamate (NCDC, a proposed inhibitor of phospholipase C) reduced both the agonist-induced 45Ca2+ influx and the sustained elevation of [Ca2+]i in the SMCs. NCDC also abolished both contraction and depolarization induced by agonists in the MRVs. The kinase C stimulator phorbol-12-myristate-13-acetate (PMA) inhibited the agonist-induced 45Ca2+ influx and sustained increase in [Ca2+]i in the SMCs, whereas the kinase C inhibitor staurosporine had no effect. In the MRVs, in contrast, PMA had no influence on agonist-induced contractions. Staurosporine (1 microM), however, completely prevented these contractions, as did NCDC, but, unlike NCDC, it did so without affecting the agonist-induced depolarization. These data support an important role of receptor-operated Ca2+-permeable channels in VSM activation by agonists and suggest that these channels may be controlled by intracellular enzymic pathways and second messenger systems.
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PMID:Receptor-operated calcium-permeable channels in vascular smooth muscle. 247 25

3H vasopressin specifically binds to the binding sites in liver, kidney and adenohypophysis with Bmax = 11.8 +/- 5.6, 1.7 +/- 0.5 and 4.9 +/- 1.2 pmol/g tissue and Kd = 1.5 +/- 0.5, 0.66 +/- 0.21 and 0.84 +/- 0.21 nM, correspondingly. Specific binding increases in the presence of Mg2+ and Ni2+ and decreases at high temperature (37 degrees). The presence of high affinity binding sites for 3H vasopressin was shown in the rat adrenals, binding was saturable and reversible. Concentration of vasopressin binding sites in adrenals is 6-8 fold less than in adenohypophysis. It is supposed that vasopressin receptors in adrenals may participate in the regulation of corticosteroid secretion.
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PMID:[Identification of specific vasopressin binding sites in cell membranes of the adenohypophysis, liver, kidney and adrenal glands of the rat]. 253 44

Lipid methylation has been studied in homogenized dog kidney cortical tubules. At pH 9, using S-adenosyl-L-methionine as methyl donor, most of the methyl groups appeared incorporated into phosphatidylcholine, the activity showing an apparent Km of 16 microM. This enzymatic activity was unchanged by the presence of the divalent cations Ca2+ or Mg2+, cAMP or cGMP. In addition, lipid methylation was also unchanged after treatment of intact tubules with angiotensin II, parathyroid hormone or vasopressin. An increased phosphatidylcholine synthesis was observed in the remnant kidney cortical tubules after uninephrectomy through an activation of phosphocholine transferase without detectable modification of lipid methylation. These findings suggest that lipid methylation is not regulated by these biochemical or functional stimuli tested in canine renal cortical tubules.
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PMID:Lipid methylation, hormone action and compensatory hypertrophy in renal cortical tubules. 254 7

Oxytocin-binding sites in the endometrium and myometrium of the non-pregnant ewe were characterized. [3H]Oxytocin bound to a single site in both tissues with high affinity; dissociation constants were determined to be 1.96 nmol/l in endometrium and 2.12 nmol/l in myometrium. Oxytocin binding was enhanced by divalent cations with a similar order of potency in both tissues: Co2+ greater than Mn2+ greater than Ni2+ greater than Mg2+ greater than Zn2+ greater than Ca2+. The endometrial and myometrial binding sites showed the same specificity for oxytocin analogues and related peptides, having high affinity for oxytocin, [Arg8]-vasopressin, [Lys8]-vasopressin, and the oxytocin-specific agonists [Gly7]-oxytocin and [Thr4,Gly7]-oxytocin. The results suggest that oxytocin receptors present in the endometrium and myometrium of the ewe are similar both to each other and to classical oxytocin receptors.
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PMID:Characterization of endometrial and myometrial oxytocin receptors in the non-pregnant ewe. 255 41

The role of Cl- and Mg+ ions has been studied on the secretory mechanism leading to the release of vasopressin from digitonin permeabilized nerve endings isolated from the rat neurohypophysis. Secretion was triggered by challenging the permeabilized nerve endings with 1.1 microM free Ca2+. Magnesium enhances secretion and its maximal effect occurred at a concentration of about 2 mM. Further increase of this divalent cation concentration however led to an inhibition of secretion. Chloride ions are necessary for the final steps in exocytosis and this effect of Cl- was inhibited by the chloride channel antagonist N144. It is concluded that in neurosecretory nerve endings magnesium and chloride ions are crucial components for exocytosis to occur.
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PMID:Chloride and magnesium dependence of vasopressin release from rat permeabilized neurohypophysial nerve endings. 260 85

The mammalian renal thick ascending limb of Henle (TAL) reabsorbs approximately 55% of the filtered magnesium; accordingly, it is the major segment involved in control of renal Mg balance. This review discusses recent evidence for passive and active transport of Mg through the paracellular and transcellular pathways of the TAL, respectively. The properties of these pathways provide a basis for understanding the factors influencing magnesium reabsorption and hormonal controls regulating Mg balance. Normally, Mg absorption is load dependent, whether delivery is altered by increasing luminal Mg concentration or increasing the flow rate into the thick ascending limb. In contrast to the luminal concentration, elevation of peritubular (plasma) Mg and Ca inhibit divalent cation absorption by mechanisms that are not entirely clear. Magnesium reabsorption in the TAL is also closely associated with NaCl absorption so that factors that influence NaCl also affect magnesium. Magnesium deficiency results in a specific and apparently intrinsic cellular adaptation to increase Mg absorption in the TAL. Our greatest understanding of hormonal controls for Mg absorption have come from recent studies using a "hormone deprived" animal model. Parathyroid hormone, calcitonin, glucagon, and antidiuretic hormone act through a common second messenger, adenosine 3',5'-cyclic monophosphate, to limit Mg excretion by enhancing active Mg transport in the TAL. The integrated actions of these hormones and possibly others provide a sensitive means of control. Clearly, recent observations, using in vivo and in vitro microperfusion studies, have altered our thinking of TAL function and indicate that Mg transport is sensitively and specifically controlled within this segment.
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PMID:Control of magnesium transport in the thick ascending limb. 264 45

1. Slowly hydrolysable analogues of GTP were introduced into hepatocytes by incubating the cells in the absence of Mg2+ and in the presence of ATP4-. Experiments using guanosine 5'-[gamma-[35S]thio]triphosphate (GTP[35S])indicated that about 50% of the GTP[S] loaded into the cells was subsequently hydrolysed. 2. In cells loaded with GTP[S] and incubated in the absence of added extracellular Ca2+ (Ca2+o), the rate of activation of glycogen phosphorylase observed after addition of 1.3 mM-Ca2+o was 250% greater than the rate observed in unloaded cells. Smaller effects (130%) were observed in cells loaded with either guanyl-5'-yl imidodiphosphate or guanosine 5-[beta-thio]diphosphate (GDP[S]). Cells loaded with adenosine 5'-[gamma-thio]triphosphate showed no increase in glycogen phosphorylase activity on addition of Ca2+o. 3. The effect of a submaximal concentration of GTP[S] on the Ca2+-induced activation of glycogen phosphorylase was additive with that of a half-maximally effective concentration of vasopressin. GTP[S] did not increase the effect of a maximally effective concentration of the hormone. 4. Cells loaded with GTP[S] exhibited an increased initial rate of 45Ca2+ exchange measured at 1.3 mM-Ca2+o. 5. GTP[S] did not affect the amount of 45Ca2+ exchanged by cells incubated at 0.1 mM-Ca2+o or the ability of vasopressin to release 45Ca2+ from these cells. 6. It is concluded that the introduction of slowly hydrolysable analogues of GTP to the liver cell cytoplasmic space stimulates the inflow of Ca2+ across the plasma membrane through a channel similar to that activated by vasopressin.
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PMID:Evidence that guanosine 5'-[gamma-thio]triphosphate stimulates plasma membrane Ca2+ inflow when introduced into hepatocytes. 264 79

1. Extracellular recordings were made from 175 spontaneously active cells in the rat coronal hypothalamic slice preparation. Reconstruction of the recording sites showed that fifteen were in the supraoptic nucleus (s.o.n.), ten in the magnocellular portion of the paraventricular nucleus (p.v.n.) which could be antidromically activated by stimulation lateral to the nucleus, seventy-seven other cells in the p.v.n. and seventy-three in the anteroventral third ventricle (a.v.3.v.) region. 2. The mean firing rates (mean +/- S.E. of mean) of the spontaneously firing cells in the s.o.n., p.v.n. and a.v.3.v. were 2.8 +/- 0.4 spikes/s, 2.9 +/- 0.2 spikes/s and 5.0 +/- 0.4 spikes/s, respectively. Antidromically identified p.v.n. cells fired spontaneously with a mean firing rate of 1.5 +/- 0.5 spikes/s. 3. Bath application of atrial natriuretic polypeptide (a.n.p.; 10(-7) M) had no effect on fifteen s.o.n. cells tested but nineteen (22%) of eighty-seven p.v.n. cells (including two of the ten antidromically activated cells) and thirty (41%) of seventy-three a.v.3.v. cells showed inhibitory responses. Three (3%) cells in the p.v.n. were excited by a.n.p. 4. The dose dependence of the response to a.n.p. was tested in two p.v.n. and five a.v.3.v. cells. As a.n.p. concentration increased, the firing rates of all seven cells generally decreased. However, one a.v.3.v. neurone was excited at low concentrations (less than 10(-8) M) but inhibited at high concentrations (10(-7) and 10(-6) M) of a.n.p. The threshold concentration to evoke inhibitory responses in the p.v.n. was 10(-10) M and in the a.v.3.v. was 10(-11) M. 5. With the exception of the two antidromically activated p.v.n. cells, the inhibitory effect of a.n.p. still persisted after synaptic transmission had been suppressed with a low-Ca2+ and high-Mg2+ medium. 6. Thirty-six cells in the a.v.3.v. were tested with both a.n.p. and angiotensin II applied at 10(-7) M. Twelve showed inhibitory responses to a.n.p. and nine showed excitatory responses to angiotensin II. In other experiments, a.n.p., angiotensin II and arginine-vasopressin were each applied to neurones in the p.v.n. Of the forty cells tested with all three peptides at 10(-7) M, seven were inhibited by a.n.p., fourteen were excited by angiotensin II and twenty were excited by arginine-vasopressin. No neurones in either the p.v.n. or a.v.3.v. were inhibited by a.n.p. and excited by angiotensin II, but four neurones in the p.v.n. were inhibited by a.n.p. and excited by arginine-vasopressin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of atrial natriuretic polypeptide on rat hypothalamic neurones in vitro. 282 64


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