UNIPROT:P01185 - FACTA Search

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Query: UNIPROT:P01185 (vasopressin)
23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Purinergic P2 receptors are present on proximal renal tubules, but their function is unknown. Because P2 agonists antagonize vasopressin-stimulated water transport in the distal tubule by inhibiting activation of adenylyl cyclase, we postulated that P2 receptor activation blocks parathyroid hormone (PTH) inhibition of phosphate uptake in proximal tubule by preventing PTH-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation. PTH inhibition of sodium-dependent phosphate uptake was attenuated by alpha,beta-methylene-ATP (AMP-CPP), a P2x receptor agonist, but not by 2-methyl-thio-ATP, a P2y receptor agonist, in a dose-dependent manner. AMP-CPP did not attenuate inhibition of phosphate uptake produced by direct activation of adenylyl cyclase with forskolin, by addition of the cAMP analogue 8-bromo-cAMP, or by inhibition of cAMP phosphodiesterase with RO-20-1724. Additionally, AMP-CPP had no effect on basal or PTH-stimulated cAMP production. As PTH also stimulates protein kinase C activation, the effect of AMP-CPP on inhibition of phosphate uptake stimulated by phorbol 12-myristate 13-acetate (PMA) was tested. AMP-CPP had no effect on PMA-induced inhibition of phosphate uptake. Pretreatment with pertussis toxin abolished the attenuating effect of AMP-CPP on PTH inhibition of sodium-dependent phosphate uptake. We conclude that activation of purinergic P2 receptors attenuates the inhibitory effect of PTH on sodium-dependent phosphate uptake by a G protein-dependent mechanism that is independent of cAMP generation protein kinase A activation, or protein kinase C activation.
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PMID:P2 purinoceptor stimulation attenuates PTH inhibition of phosphate uptake by a G protein-dependent mechanism. 757 78

Previous studies have demonstrated that the number of vasopressin (VP) neurons present in primary diencephalic cultures can be markedly augmented by treatment with drugs that elevate intracellular cAMP. To evaluate the effect of this drug treatment on VP secretion by hypothalamic cultures and to determine if this represents a developmental phenomenon or a mechanism involved in the continuing dynamic regulation of the VP gene, we have exposed primary dispersed hypothalamic cultures derived from 14-day-old fetal Sprague-Dawley rats to forskolin (25 microM) and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX; 500 microM), either continually or intermittently, for up to 39 days. Culture medium was collected throughout the culture period for VP RIA, and at the end of the culture period, cultures were stained immunocytochemically for neurophysin (NP). As reported by previous investigators, exposure to the drugs for 11 days resulted in an increase in the number of NP-positive neurons. The increase was sustained with longer periods of exposure up to 39 days. IBMX and forskolin treatment also resulted in detectable release of VP into the culture medium, which increased from 1.4 +/- 0.15 pg/ml at 11 days to 8.4 +/- 0.6 pg/ml after 32 days of drug treatment. The VP concentration remained undetectable (< 1.25 pg/ml) in nontreated cultures throughout this period. The effect on VP expression did not require immediate exposure to the drugs in culture, but did require the continuous presence of the drugs. Removal of the drugs from days 11-18 of culture resulted in an almost complete loss of NP-positive cells; however, reexposure to the drugs reinstated NP expression in a time-dependent fashion. The effect of IBMX/forskolin treatment on the expression of other neuronal markers was also evaluated. The treatment did not alter the total number of neurons, and there was no evidence of stimulation of oxytocin expression. There was a marked increase in the number and size of neurons stained immunocytochemically for tyrosine hydroxylase and a small increase in the number of cells staining for somatostatin. These results demonstrate that treatment with cAMP-elevating drugs markedly and selectively elevates VP secretion from dispersed hypothalamic cultures, but continuous exposure to the drugs is necessary to sustain the effect. These findings suggest that although cAMP is required in hypothalamic cultures for VP gene expression, it may also participate in the dynamic regulation of VP gene transcription in response to physiological challenges.
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PMID:The stimulation of vasopressin gene expression in cultured hypothalamic neurons by cyclic adenosine 3',5'-monophosphate is reversible. 768 52

The anti-ischemic effects of a new, selective and potent cyclic 3',5'-guanosine monophosphate-specific phosphodiesterase (phosphodiesterase type V) inhibitor, sodium 1-[6-chloro-4-(3,4-methylenedioxybenzyl)aminoquinazolin-2-yl ]piperidine-4- carboxylate (E4021), in a vasopressin-induced guinea pig anginal model were examined and compared with those of coronary vasodilators with a guanylate cyclase-activating action. An intravenous injection of vasopressin (0.2 IU/kg) into anesthetized guinea pigs produced ST segment elevation on the electrocardiogram (an index of myocardial ischemia) of 0.28 +/- 0.02 mV (n = 10) from the baseline within 30 s. E4021 administered intravenously at doses of 0.03 and 0.1 mg/kg, 5 min before the injection of vasopressin, significantly inhibited the ST segment elevation to 0.15 +/- 0.03 mV (n = 6, P < 0.01) and 0.17 +/- 0.02 mV (n = 6, P < 0.01), respectively. Three guanylate cyclase activators, isosorbide dinitrate (0.1 mg/kg), nicorandil (0.1 mg/kg), and FK409 (0.3 mg/kg), also significantly reduced the ST segment elevation to 0.18 +/- 0.03, 0.11 +/- 0.02 and 0.17 +/- 0.02 mV, respectively. In a second experiment, E4021 was administered intraduodenally 30 min before the injection of vasopressin to examine its oral effectiveness. Intraduodenal E4021, at doses of 1.0 and 3.0 mg/kg, also significantly inhibited the ST segment elevation to 0.16 +/- 0.02 mV (n = 6, P < 0.01) and 0.13 +/- 0.02 mV (n = 6, P < 0.01), respectively. It is concluded that the potent phosphodiesterase type V inhibitor, E4021, administered intravenously or intraduodenally, ameliorated myocardial ischemia similarly to guanylate cyclase activators. Thus, E4021 may be an orally effective drug in the treatment of angina pectoris.
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PMID:Effects of a novel, selective and potent phosphodiesterase type V inhibitor, E4021, on myocardial ischemia in guinea pigs. 782 68

Although prevention of heart failure recently has become a realistic issue, management of heart failure once the syndrome has developed, is mainly supportive, based on the various cardiac and peripheral changes which occur in the course of heart failure. Of these, abnormal neurohormonal activation is of major pathophysiologic and prognostic significance. Consequently, modulation of neuroendocrine activation is now recognized a prime target in the treatment of heart failure, besides diuretic therapy. In this respect, the value of converting enzyme inhibition is well established. Future developments in this area include dopaminergic agents, vasopressin antagonists, angiotensin II receptor antagonists, renin inhibitors, spironolactone and, possibly, ANF peptidase inhibitors. Besides diuretics, necessary when signs of fluid retention are present, the approach to heart failure management involves other pharmacologic issues. In view of abnormal vascular control with vasoconstriction prevailing during progressive heart failure, it clearly makes sense to vasodilate. However, of available vasodilators, only the combination of relatively high dose nitrates and hydralazine has proven to be of clinical significance, in terms of hemodynamics, exercise capacity and survival. It is possible, though, that novel generation dihydropyridine derivatives may prove beneficial as well. Thus far, there has been much debate concerning the usefulness and particularly the safety of positive inotrope therapy and inodilator treatment. Taken together, this concern relates to presence and predominance of cAMP-dependent mechanisms to induce these effects. Thus, sympathomimetic agents and phosphodiesterase inhibitors, such as milrinone or enoximone, are without beneficial effects, but instead shorten survival during long-term therapy. This may be different where compounds which act through cAMP-independent mechanisms, i.e., calcium sensitization or sodium channel stimulation, are concerned, but needs to be confirmed yet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Congestive heart failure. Drug therapy: central or peripheral approach? 791 52

We examined effects of a novel antidiabetic agent, racemic englitazone (CP 68,722, Pfizer), on normal rat hepatocytes in vitro. For optimal effects, CP 68,722 must be preincubated for approximately 20 minutes. CP 68,722 inhibited the actions of glucagon on glycogenolysis (measured by monitoring cyclic adenosine monophosphate [cAMP] levels, phosphorylase activation, and glucose output) and gluconeogenesis (from 14C-lactate). Since CP 68,722 was able to attenuate the ability of glucagon to increase cAMP levels, this may account for part of its inhibitory actions on glycogenolysis and gluconeogenesis. The observation that CP 68,722 also inhibits the ability of the cAMP analog, 8-(4-chlorophenylthio)-adenosine 3':5'-cyclic monophosphate (8 CPT cAMP), to stimulate phosphorylase a is consistent with an effect of CP 68,722 to activate cAMP-dependent phosphodiesterase. The ability of vasopressin (an agonist known to stimulate glycogenolysis via a Ca(2+)-dependent mechanism) to stimulate phosphorylase a was slightly inhibited by CP 68,722. Another site of action of CP 68,722 was to inhibit hormonal-mediated Ca2+ influx, an effect that would decrease intracellular free calcium ([Ca2+]i), thereby inhibiting the actions of the Ca(2+)-dependent hormones such as alpha 1-adrenergic agonists and vasopressin, agents known to promote glucose output from the liver. In summary, CP 68,722 inhibits glucagon-stimulated glycogenolysis and gluconeogenesis in hepatocytes by a mechanism that may include activation of cAMP phosphodiesterase and inhibition of Ca2+ influx.
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PMID:Actions of the novel antidiabetic agent englitazone in rat hepatocytes. 824 73

The DI +/+ Severe hereditary nephrogenic diabetes insipidus mouse is resistant to the antidiuretic action of vasopressin (VP) because of failure to accumulate cAMP and subsequent inability to form intramembranous particles on the apical (luminal) surface of kidney cells that normally respond to VP. The defect is primarily, if not exclusively, due to excessive activity of specific cAMP-phosphodiesterases. The abnormality can be overcome in vitro and in vivo by the phosphodiesterase inhibitor, rolipram. Most cases of hereditary NDI in man have sex-linked recessive inheritance, which appears to be due to an abnormality of the V2 receptor. The chromosomal locus of the defect is Xq28. Sporadic cases of congenital NDI have been described in females who appear to have a defect beyond the V2 receptor and the guanine nucleotide-binding stimulatory protein. There is no information on the biochemical defect in very rare cases with other types of inheritance patterns. No abnormalities of V1a and V1b receptor function have been found in patients with NDI. Mice and patients with NDI have evidence of increased AVP synthesis. AVP release in relation to plasma osmolality is increased in patients during infusion of hypertonic saline. This is the opposite of what has been described in patients with primary polydipsia (dipsogenic diabetes insipidus) who are chronically overhydrated. Together, these studies indicate that chronic dehydration and overhydration can cause up- and downregulation of the osmotic release of AVP.
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PMID:Hereditary vasopressin resistance in man and mouse. 837 15

The studies of animal models of nephrogenic diabetes insipidus (NDI) suggest that abnormally high activity of cAMP phosphodiesterase (cAMP-PDE), may cause unresponsiveness to the diuretic effect of AVP. We explored whether overexpression of one of the cAMP-PDE type isozymes, PDE-IV, in [8-Arg]-vasopressin (AVP) sensitive renal epithelial LLC-PK1 cells can prevent the hormone-elicited cAMP increase. LLC-PK1 cells were stably transfected with ratPDE3.1 cDNA (which encodes for rolipram-sensitive PDE-IV), inserted in plasmid pCMV5 and then were compared with sham-transfected LLC-PK1 cells and wild LLC-PK1 cells. In the stably transfected clone (LLC-PK1-S #16), the rolipram-sensitive PDE-IV activity was about five times higher than in controls, whereas activities of other types of PDEs were not different. The presence of cognate mRNA for PDE-IV was confirmed by Northern blot. Whereas in the control cells (wild LLC-PK1 cells and sham-transfected LLC-PK1 cells), the incubation with 10(-7) M AVP increased cAMP more than tenfold, the LLC-PK1-S#16 cells with overexpressed cAMP-PDE were resistant to cAMP-increasing effects of AVP and forskolin. However, in the same LLC-PK1-S#16 cells the cGMP increases in response to nitroprusside were not diminished. The AVP-dependent cAMP accumulation in LLC-PK1-S#16 cells with overexpressed PDE-IV was restored by addition of roliprams which decreased cAMP-PDE activity to the levels similar to those in wild LLC-PK1 cells and sham-transfected LLC-PK1-#A1 cells. In contrast, inhibitors of other PDE isozymes (PDE-I or PDE-III) had little or no effect. Our findings show that excessive activity of cAMP-PDE, in this case of isozyme PDE-IV, can cause resistance to AVP which is analogous to that observed in collecting ducts of mice with hereditary nephrogenic diabetes insipidus.
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PMID:ADH resistance of LLC-pk1 cells caused by overexpression of cAMP-phosphodiesterase type-IV. 839 Oct 97

In an attempt to determine if PACAP synergistically interacts with vasopressin (VP) and protein kinase C (PKC) to enhance cyclic AMP formation and adrenocorticotrophic hormone (ACTH) secretion, the effects of PACAP, either alone or together with VP and the phorbol ester phorbol 12-myristate 13-acetate (PMA) were examined in primary cultures of rat anterior pituitary cells. VP failed to potentiate the stimulatory effect of PACAP on cyclic AMP formation, while it dramatically enhanced the effect of corticotropin-releasing factor (CRF). However, activation of PKC upon exposure of cells to PMA amplified cyclic AMP production induced by both peptides, though in the case of PACAP, contrary to that of CRF, potentiation was markedly dependent on the blockade of phosphodiesterase (PDE) activity, for it was undetectable in the absence of the inhibitor Rolipram. Depletion of PKC by long-term treatment of pituitary cells with PMA abolished the synergistic influence of PMA. There was no significant effect of PACAP, either alone or together with PMA, on ACTH secretion, while PMA enhanced peptide secretion elicited by CRF. The data show that in anterior pituitary cells cyclic AMP accumulation induced by PACAP and CRF was differentially modulated by PKC and PDE activities and that the potentiation of PACAP-stimulated cyclic AMP accumulation by PMA was not reflected by parallel increment of ACTH secretion.
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PMID:Vasopressin, unlike phorbol ester, fails to synergistically interact with pituitary adenylate cyclase activating polypeptide (PACAP) in stimulating cyclic AMP formation and ACTH secretion in cultured anterior pituitary cells. 839 88

To determine the molecular steps involved in the vasopressin-induced renal Na+ reabsorption, the patch-clamp technique was utilized to study the role of this hormone in the regulation of apical Na+ channels in renal epithelial A6 cells. Addition of arginine vasopressin (AVP) induced and/or enhanced Na+ channel activity within 5 min of addition under cell-attached conditions. The AVP-induced channel activity was a reflection of both an increase in the average apparent channel number (0.2-1.7) and the percent open time (2-56%). Addition of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, the adenosine 3',5'-cyclic monophosphate (cAMP) analogues, 8-(4-chlorophenylthio)-cAMP and 8-bromo-cAMP, or forskolin elicited a comparable effect to that of AVP. The induced channels had similar properties to Na+ channels previously reported, including a channel conductance of 9 pS, Na(+)-to-K+ selectivity of 3-5:1, and high amiloride sensitivity. The cAMP-dependent protein kinase A (PKA) in the presence of ATP induced and/or enhanced Na+ channel activity in excised inside-out patches with a change in average apparent channel number and percent open probability similar to those observed with either AVP or cAMP analogues in intact cells. Addition of activated pertussis toxin (100 ng/ml) completely blocked the AVP- or PKA-induced Na+ channel activity in excised inside-out patches, whereas incubation of intact cells with the toxin completely prevented the effect of both activators. The data indicate that AVP mediates its effect through a cAMP-dependent pathway involving PKA activation whose target is the G protein pathway that regulates apical epithelial Na+ channel activity.
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PMID:Vasopressin and protein kinase A activate G protein-sensitive epithelial Na+ channels. 839 79

Hydroosmotic effect of vasopressin enhanced by the addition of hydrocortisone to serosal Ringer solution of frog urinary bladder. The osmotic permeability of the urinary bladder wall increased after inhibition of cAMP phosphodiesterase by isobutylmethylxanthine followed by the addition of cAMP; hydrocortisone modulated the action of cAMP phosphodiesterase and consequently increased the effect of isobutylmethylxanthine.
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PMID:[The enhancement by hydrocortisone of the hydro-osmotic effect of vasopressin and cAMP in the frog bladder wall]. 840 Jan 71

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