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)

Cyclic AMP plays a major, if not primary, role in the regulation of hepatic gluconeogenesis. The cyclic nucleotide acts on two levels. First, cAMP levels determine the phosphorylation state of key regulatory enzymes including pyruvate kinase and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. Regulation of cAMP levels by glucagon, insulin, and catecholamines accounts in large part for minute-to-minute hormonal control of pathway flux in fed animals and during the transition from fed to starved; second, cAMP plays a key role in regulation of gene transcription of phosphoenolpyruvate carboxykinase, pyruvate kinase, glucokinase, and probably 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. Cyclic AMP acts to induce synthesis of mRNA for phosphoenolpyruvate carboxykinase and probably fructose 1, 6-bisphosphatase while it suppresses transcription of the genes for pyruvate kinase and glucokinase. Its role in the regulation of gene transcription of the bifunctional enzyme and 6-phosphofructo 1-kinase remains to be defined. Insulin is the most important hormone for restraining the level of cAMP. Insulin acts to oppose the acute actions of cAMP on enzyme phosphorylation, presumably by activating a phosphodiesterase and thereby lowering cAMP levels. Insulin also opposes the action of hormones (alpha-adrenergic agonists, angiotensin, vasopressin) that act in liver via cAMP-independent phosphorylation. However, in the systems in which this has been studied, the cAMP-independent effects on gluconeogenic/glycolytic pathway flux are small in comparison to cAMP-dependent regulation. Insulin also opposes the action of cAMP on gene transcription by an as yet unknown mechanism. This effect does not appear to involve changes in the level of cAMP because the hormone also acts in cultured cells when added alone or in the presence of dexamethasone. The ability of insulin to lower hepatic cAMP levels and to modulate gene expression are important because restoration of acute regulatory hormone responsiveness to starved or diabetic animals could not occur if insulin were unable to lower cAMP levels and be the dominant factor in modulating the gene expression of these key regulatory enzymes. Clearly, the hepatic gluconeogenic/glycolytic pathway undergoes a complex but extremely well-integrated regulation by hormones that accounts in large part for the major role the organ plays in the control of glucose homeostasis.
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PMID:The role of cyclic AMP in rapid and long-term regulation of gluconeogenesis and glycolysis. 285 23

The peak hemodynamic effect and hormonal response of the phosphodiesterase inhibitor enoximone (MDL 17,043) were compared with those of dobutamine in 10 patients with severe congestive heart failure. Both agents significantly (p less than 0.05) increased cardiac index, stroke volume index and heart rate. Enoximone tended to decrease mean systemic arterial and pulmonary artery wedge pressures (0.05 less than p less than 0.1), whereas dobutamine did not. Both agents decreased systemic vascular resistance (p less than 0.05). The increase in heart rate was greater with dobutamine than with enoximone (p less than 0.05). Plasma renin activity increased significantly with dobutamine (from 11.3 +/- 13.5 to 17.8 +/- 15.0 ng/ml/hour, p less than 0.01) and with enoximone (from 13.6 +/- 18.3 to 16.6 +/- 18.8 ng/ml/hour, 0.05 less than p less than 0.1). Dobutamine suppressed plasma norepinephrine level (p less than 0.05) and enoximone did not. Neither agent affected the plasma vasopressin level. These data demonstrate a similar acute hemodynamic and hormonal profile for both enoximone and dobutamine. Further, dobutamine, like other beta agonists, provokes renin secretion and may do so to a greater extent than enoximone.
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PMID:Comparative hemodynamic and hormonal response of enoximone and dobutamine in severe congestive heart failure. 294 27

A polyuric syndrome with nephrogenic diabetes insipidus (NDI) is a frequent consequence of prolonged administration of lithium (Li) salts. Studies in the past, mainly the acute and in vitro experiments, indicated that Li ions can inhibit hydroosmotic effect of [8-arginine]vasopressin (AVP) at the step of cAMP generation in vitro. However, the pathogenesis of the NDI due to chronic oral administration of low therapeutic doses of Li salts is not yet clarified. We conducted a comprehensive study to clarify the mechanism by which Li administered orally for several weeks induces polyuria and NDI in rats. Albino rats consuming a diet which contained Li (60 mmol/kg) for 4 wk developed marked polyuria and polydipsia; at the end of 4 wk the plasma Li was 0.7 +/- 0.09 mM (mean +/- SEM; n = 36). Li-treated rats had a significantly decreased (-33%) tissue osmolality in papilla and greatly reduced cortico-papillary gradient of urea (cortex--43%; medulla--64%; papilla--74%). Plasma urea was significantly (P less than 0.001) lower in Li-treated rats (5.4 +/- 0.2 mM) compared with controls (6.8 +/- 0.3 mM). Medullary collecting tubules (MCT) and papillary collecting ducts (PCD) microdissected from Li-treated animals had higher content of protein than MCT and PCD from the control rats. The cAMP accumulation in response to AVP added in vitro was significantly (delta = -60%) reduced. Also, the cAMP accumulation in MCT and PCD after incubation with forskolin was markedly lower in Li-treated rats. Addition of 0.5 mM 1-methyl,3-isobutyl-xanthine did not restore the cAMP accumulation in response to AVP and forskolin in MCT from Li-treated animals. In collecting tubule segments from polyuric rats with hypothalamic diabetes insipidus (Brattleboro homozygotes) the AVP-dependent cAMP accumulation was not diminished. The activity of adenylate cyclase (AdC) in MCT of Li-treated rats, both the basal and the activity stimulated by AVP, forskolin, or fluoride, was significantly (delta approximately equal to -30%) reduced, while the activity of cAMP phosphodiesterase (cAMP-PDIE) in the same segment showed no significant difference from the controls. Also, the content of ATP in MCT microdissected from Li-treated rats and incubated in vitro did not differ from controls. The rate of [14C]succinate oxidation to 14CO2 in MAL was inhibited (-77%) by 1 mM furosemide, which indicates that this metabolic process is coupled with NaCl cotransport in MAL. The rate of (14)CO(2) production from [14C]succinate in MAL was not significantly different between control and Li-treated rats. In MCT of control rats, the rate of [14C]succinate oxidation was approximately 3 times lower than in MAL. The rate of (14)CO(2) production from [(14)C]succinate in MCT of Li-treated rats was significantly (delta +33%) higher than in MCT dissected from control rats. Based on these results, we conclude that at least two factors play an important role in the pathogenesis of NDI consequent to chronic oral administration of Li: (a) decreased ability of MCT and PCD to generate and accumulate cAMP in response to stimulation by AVP; this defect is primarily due to diminished activity of AdC in these tubular segments caused by prolonged exposure to Li; and (b) lower osmolality of renal papillary tissue, due to primarily to depletion of urea, which decreases osmotic driving force for water reabsorption in collecting tubules. On the other hand, NaCI reabsorption in MAL is apparently not affected by chronic Li treatment.
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PMID:Pathogenesis of nephrogenic diabetes insipidus due to chronic administration of lithium in rats. 298 35

The factors responsible for the urinary concentrating defect associated with the potassium-depleted (KD) state are uncertain. The present studies were designed to, first, determine whether a urinary concentrating defect exists in potassium-depleted rabbits and, second, to use the technique of in vitro perfusion to evaluate directly the antidiuretic hormone (ADH) responsiveness of cortical collecting tubules (CCT) in this setting. Feeding female New Zealand White rabbits a potassium-deficient diet for 2 wk caused a significant fall in plasma potassium levels in both the ad-libitum and controlled water intake groups (P less than 0.001). Muscle potassium content after 2 wk of potassium restriction fell from 45.6 +/- 0.9 to 29.0 +/- 1.2 meq/100 g fat-free dry solids (P less than 0.001). Renal papillary sodium content fell significantly from a control value of 234.6 +/- 8.0 to 182.46 +/- 10.0 meq/kg H2O after 2 wk of potassium restriction. Maximal urinary osmolality measured after 12 h of dehydration and 1.25 U pitressin IM was significantly decreased in rabbits after 2 wk of potassium restriction in both the ad-libitum and controlled water intake groups (P less than 0.001). The relationship between plasma potassium concentration and maximum urinary osmolality was significantly correlated in both the ad-libitum and controlled water intake groups, r = 0.73 and 0.68 (P less than 0.001), respectively. In addition, refeeding KD rabbits with normal chow for 1 wk resulted in normalization of both plasma potassium levels and urinary concentrating ability. CCT from control and KD rabbits were perfused in vitro at 25 degrees C. The hydraulic conductivity coefficient, Lp, was significantly reduced at all doses of ADH tested in tubules from KD rabbits when compared with control tubules. In addition, the maximal hydraulic conductivity in tubules from KD rabbits when tested with 200 microU/ml ADH at 37.5 degrees C was only 23% of control values (P less than 0.05). Furthermore, this reduced ADH responsiveness persisted when the bath potassium was elevated from 5 to 20 mM. The reflection coefficient for NaCl when compared with raffinose was 0.91 in tubules from KD animals. Thus, these data suggest that the ADH-resistant urinary concentrating defect associated with potassium depletion is due, at least in part, to a diminished responsiveness of the CCT to ADH. Therefore, further studies were designed to investigate the cellular steps involved in this abnormal response. There was no difference in the 8-para-chlorophenylthio cyclic AMP induced hydroosmotic response between CCT from KD and control rabbits. Since the cAMP-induced hydroosmotic response was similar between KD and control CCT, experiments were performed to evaluate the contribution of phosphodiesterase (PDIE) activity by using the potent PDIE inhibitor isobutylmethylxanthine (10(-4) and 10(-3)M) in the presence of ADH (200 U/ml). Although Lp was increased by PDIE inhibition in CCT from both control and KD animals, the overall hydroosmotic response in CCT from KD rabbits was still significantly reduced when compared with controls. The final experiments used forskolin to evaluate further the adenylate cyclase complex. The resulting hydroosmotic response in CCT from KD rabbits was almost identical to that obtained in controls. In conclusion, these data suggest that the decreased responsiveness of CCT from KD rabbits to ADH involves a step at or proximal to the stimulation of the catalytic subunit of adenylate cyclase, and that PDIE activity makes no contribution to this abnormal hydroosmotic response.
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PMID:In vivo and in vitro studies of urinary concentrating ability in potassium-depleted rabbits. 299 61

Purinergic agonists cause a dose-dependent activation of glycogen phosphorylase in isolated rat hepatocytes. Half-maximally effective concentrations are 5 X 10(-7)M for ATP, 2 X 10(-6)M for ADP, and about 5 X 10(-5) M for AMP and adenosine. This potency series indicates the presence of P2-purinergic receptors. The mode of action of ATP appears to be identical with that of the Ca2+-dependent glycogenolytic hormones angiotensin, vasopressin and alpha 1-adrenergic agonists. (1) They all require Ca2+ for phosphorylase activation; (2) they do not increase cyclic AMP levels; (3) they are susceptible to heterologous desensitization by vasopressin and phenylephrine; (4) they lower cyclic AMP concentrations in hepatocytes stimulated by glucagon, most probably mediated by an enhanced phosphodiesterase activity.
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PMID:P2-purinergic control of liver glycogenolysis. 300 Mar 60

A mutant LLC-PK1 cell line, M18, was isolated after a single treatment of the parent culture with N-methyl-N'-nitro-N-nitroso-guanidine. In contrast to LLC-PK1 cells, the mutant did not exhibit production of urokinase-type plasminogen activator (uPA) in response to the hormones calcitonin and vasopressin, but produced the expected levels of uPA upon stimulation by the receptor-independent adenylate cyclase activators forskolin and cholera toxin, as well as by the phosphodiesterase inhibitor isobutylmethylxanthine and the 8-bromo analogue of adenosine cyclic monophosphate, Br8cAMP. The patterns of activation of cAMP-dependent protein kinase were identical to those of uPA induction: calcitonin and vasopressin were without effect, but the response to all other agents was normal. In similar fashion, mutant cell homogenates displayed normal activation of adenylate cyclase upon treatment with sodium fluoride, forskolin, or the non-hydrolyzable GTP analogue guanosine 5'-[beta, gamma-imino]triphosphate, but were unresponsive to calcitonin or vasopressin. The ability of M18 cells to bind radioactively labelled calcitonin and vasopressin was measured. The mutant possessed less than 4% of the normal levels of the receptor binding activity for both hormones. Somatic cell hybrids formed between M18 and LLC-PK1 cells were found to retain normal hormone binding activity and responsiveness to hormones, indicating that the defect in M18 cells was recessive. M18 was concluded most probably to contain a single mutation impairing the function of two distinct polypeptide hormone receptors.
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PMID:Isolation of a mutant LLC-PK1 cell line defective in hormonal responsiveness. A pleiotropic lesion in receptor function. 302 58

In decapod crustaceans steroidogenic glands (Y-organs) produce the molting hormone, ecdysone. A putative neuropeptide, molt-inhibiting hormone (MIH), released from eyestalk neurosecretory cells, directly regulates Y-organs by suppressing steroidogenesis; the effect is mediated by an increase in cAMP. We explored calcium-cAMP interactions in the regulation of Y-organs in vitro of the crab, Cancer antennarius. Basal ecdysteroid production was enhanced by extracellular calcium (EC). MIH suppression did not require EC but its action was blocked by high EC. The inhibitors of Ca2+ flux, lanthanum and ruthenium red, mimicked and enhanced MIH action. Calcium ionophore A23187 raised basal steroidogenesis dose-dependently (10(-6) to 10(-4) M) and with time course (effect evident after 2 h) similar to that of suppression by MIH. Low EC enhanced the suppressive effects on steroidogenesis of forskolin and dibutyryl cyclic AMP ((Bu)2cAMP) but not of MIH, lysine vasopressin (LVP), or 3-isobutyl-1-methyl-xanthine (IBMX); basal Y-organ cAMP levels were elevated by low EC and reduced by A23187. A23187 reduced the steroidogenic-suppressive effects of MIH, LVP, forskolin and (Bu)2cAMP but not of IBMX; rises in cAMP induced by MIH, LVP, and forskolin but not by IBMX were blunted by A23187. These findings suggested a stimulatory action of calcium on phosphodiesterase (PDE). The calmodulin (CM) inhibitor trifluoperazine (TFP; 10(-5) to 10(-4) M) reduced basal and A23187-stimulated steroidogenesis, enhanced the inhibitory effects of MIH and (Bu)2cAMP on ecdysteroid production, enhanced the stimulatory effects of MIH and forskolin on cAMP, and blocked the inhibition of cAMP by A23187. Y-organ PDE activity was enhanced by increasing free Ca2+ (10(-7) to 10(-5) M) and inhibited by TFP (10(-5) to 10(-4) M). Adenylate cyclase activity of Y-organ cell particulate fraction was unaffected by Ca2+ or TFP. Calcium stimulates steroidogenesis, apparently by activating a calcium-CM-dependent cAMP-PDE: the action is counter to the cAMP-mediated MIH-inhibitory system. Ca2+ fluxes were measured with dispersed Y-organ cells, in the presence and absence of agents that alter cAMP levels. The ionophore A23187, but not MIH or forskolin, increased 45Ca2+ entry by 45% over untreated control cells. Efflux from 45Ca2+-preloaded cells was increased 30% by MIH and forskolin, but not A23187. These data, together with those further above, suggest that MIH suppresses steroidogenesis in part by fostering Ca2+ depletion, and that the effect is mediated by cAMP.
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PMID:Regulation of crab Y-organ steroidogenesis in vitro: evidence that ecdysteroid production increases through activation of cAMP-phosphodiesterase by calcium-calmodulin. 302 69

The present study was undertaken to investigate the cAMP system in isolated vasopressin (AVP)-sensitive segments of the hypercalcemic rat. Hypercalcemia was produced by supplementation of diet with dihydrotachysterol, achieving a mean serum calcium of 12.6 mg%. Maximal urinary concentration was only 1982 +/- 119 mOsm/kg H2O in pair, watered hypercalcemic rats when compared to 2478 +/- 93 mOsm/kg H2O in controls (N = 7) (P less than 0.01). Vasopressin stimulated adenylate cyclase activity at concentrations of vasopressin between 10(-9) and 10(-7) M was indistinguishable in the outer medullary collecting duct (OMCD) and inner medullary collecting duct (IMCD) of tubules dissected from hypercalcemic rats or normocalcemic rats. Likewise, in situ cAMP accumulation in response to 10(-7) M AVP was not significantly different in either OMCD or IMCD of hypercalcemic or normocalcemic rats at either isotonic or hypertonic media conditions. In contrast, while 10(-7) M AVP significantly (P less than 0.05) increased cAMP accumulation in the medullary ascending limb (MAL) of normocalcemic rats it failed to do so in the MAL of hypercalcemic rats. This failure to accumulate cAMP appears to be due to impairment in AVP-stimulated adenylate cyclase rather than to enhanced phosphodiesterase activity. A similar decrement in glucagon stimulated adenylate cyclase occurred with 10(-6) M glucagon. The results demonstrate that in chronic hypercalcemia the cAMP system in the OMCT and IMCD of the rat is intact, but the MAL demonstrates abnormal AVP responsiveness due to impaired adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The cAMP system in vasopressin-sensitive nephron segments of the vitamin D-treated rat. 303 55

Human pregnancy is characterized by a blunted pressor responsiveness to vasopressor substances. This was first reported by Dieckmann and Michel in 1937 in experiments in which they measured vascular reactivity to the pressor effects of a crude preparation of vasopressin. Recently, this has been reported to occur in response to epinephrine, norepinephrine (NE), and angiotensin II (AII). Gant and associates reported that the increasing vascular sensitivity to infused AII not only was characteristic of women who developed pregnancy-induced hypertension, but in fact preceded the development of pregnancy-induced hypertension. Although a variety of factors may mediate this blunted pressor responsiveness, the most likely candidate appears to be the localized production within endothelium and/or vascular smooth muscle of prostaglandins. Indeed, administration of indomethacin or aspirin results in an increased sensitivity to infused AII in normotensive previously AII-refractory women. Administration of the steroid hormone 5 alpha-dihydroprogesterone reverses this apparent prostaglandin-mediated response. In addition, administration of the phosphodiesterase inhibitor, theophylline, results in a restoration of vascular refractoriness to infused AII in women with pregnancy-induced hypertension or in women destined to develop pregnancy-induced hypertension. Although a variety of known and possibly unknown compounds might also effect the control of vascular reactivity during human pregnancy, the prostinoids appear to play a pivotal role in mediation of control of vascular reactivity during human pregnancy.
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PMID:Control of vascular reactivity in pregnancy. 355 2

Arginine vasotocin (AVT) caused a concentration-dependent increase of glycogen phosphorylase alpha activity, breakdown of glycogen and release of glucose, when added to pieces of axolotl liver in organ culture. The concentration causing half-maximal response (EC50) was about 1 nmol/l. These actions of AVT were unaffected by the adrenergic antagonists propranolol, yohimbine and prazosin, but were blocked by equimolar amounts of d(CH2)5Tyr(Me)AVT, a synthetic antagonist of vasopressin. Arginine vasotocin similarly caused glycogenolysis in isolated perfused axolotl liver where the EC50 was about 0.1 nmol/l. The glycogenolytic action of AVT (10 nmol/l) was sustained for at least 3 h in Ca2+-free perfusion and longer in organ culture. No increase in Ca2+ concentration in the effluent perfusion medium was apparent during AVT-induced glucose release. Omission of Ca2+ from the medium, together with addition of EGTA (2.5 mmol/l) to the organ culture, had only a slight inhibitory effect upon the rate of glycogenolysis brought about by AVT and did not inhibit the glycogenolytic action of catecholamines. Addition of the calcium ionophore A23187 (5 mumol/l) neither caused glucose release nor abolished the glycogenolytic action of AVT added subsequently. Nevertheless, A23187 caused increased loss of 45Ca from Ca2+-loaded liver pieces whereas AVT was without effect. There was a slight accumulation of cyclic AMP (cAMP), but not cGMP, in axolotl liver pieces cultured in the presence of 0.1 mumol AVT/l and this was accentuated in the presence of phosphodiesterase inhibitors. We conclude that, in contrast to the position in mammals, Ca2+ is not involved in the glycogenolytic actions of AVT or catecholamines in axolotl liver. Preliminary experiments suggest that the same is true in the carp and we suggest that the involvement of Ca2+ in regulation of hepatic glucose release may not have evolved until after the amphibians separated from the ancestors of the mammals.
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PMID:Calcium-independent stimulation of glycogenolysis by arginine vasotocin and catecholamines in liver of the axolotl (Ambystoma mexicanum) in vitro. 370 Dec 46

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