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)

The major action of forskolin, the diterpine activator of adenylate cyclase, in primary (unpassaged) rat aortic smooth muscle cells is to reduce vasopressin-stimulated Ca2+ concentrations. In repetitively passaged cells, however, forskolin by itself increased Ca2+ levels by apparently stimulating Ca2+ uptake into the cell and had much smaller effects on inhibiting vasopressin-stimulated Ca2+ elevations. Both primary and passaged smooth muscle cells contained adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. Guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase was greatly reduced or absent in passaged smooth muscle cells. The introduction of purified cGMP-dependent protein kinase into the cytoplasm of passaged cells prevented forskolin from elevating intracellular Ca2+ and restored the capacity of forskolin to reduce vasopressin-stimulated Ca2+ mobilization. Similar effects were observed for isoproterenol in passaged smooth muscle cells. When introduced into cells, the active catalytic subunit of the cAMP-dependent protein kinase did not lead to reductions in Ca2+ levels. These results suggest that cAMP elevations lead to profound changes in Ca2+ metabolism through activation of both cAMP- and cGMP-dependent protein kinases. Activation of cGMP-dependent protein kinase by cAMP leads to the reduction in intracellular Ca2+, whereas activation of cAMP-dependent protein kinase may only mediate the uptake of Ca2+ from extracellular sources.
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PMID:cGMP-dependent protein kinase mediates the reduction of Ca2+ by cAMP in vascular smooth muscle cells. 215 36

Primary rat aortic cells, when treated with arginine vasopressin or depolarizing concentrations of K+, responded to atriopeptin II and 8-bromo-cGMP (8-Br-cGMP) with decreases in intracellular Ca2+ levels. The effects of atriopeptin and 8-Br-cGMP were diminished in cells which had been passaged many times. Low levels of cGMP-dependent protein kinase were present in soluble extracts prepared from the unresponsive cells in later passage compared with extracts from responsive cells. Unresponsive cells, when induced to incorporate cGMP-dependent protein kinase into the cytoplasm using the osmotic lysis procedure of Okada and Rechsteiner (Okada, C. Y., and Rechsteiner, M. (1982) Cell 29, 33-41), responded to atriopeptin and 8-Br-cGMP with reductions in peak Ca2+ levels in response to vasopressin and depolarizing concentrations of K+. Cells which were furnished with affinity-purified antibody to the cGMP-dependent protein kinase after the introduction of the kinase remained unresponsive to the effects of atriopeptin. In addition, antibody furnished to responsive primary cultured cells inhibited the effects of atriopeptin and 8-Br-cGMP on Ca2+ levels. These data suggest that repetitively passaged cultured rat aortic smooth muscle cells lose their responsiveness to cGMP concurrently with the loss of cGMP-dependent protein kinase. Restoration of kinase to the cells results in the restoration of responsiveness to cGMP. Thus cGMP-dependent protein kinase appears to be the mediator of the reduction in Ca2+ levels upon elevation of intracellular cGMP.
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PMID:Regulation of intracellular Ca2+ levels in cultured vascular smooth muscle cells. Reduction of Ca2+ by atriopeptin and 8-bromo-cyclic GMP is mediated by cyclic GMP-dependent protein kinase. 253 16

Nitric oxide has a diuretic effect in vivo. We have shown that nitric oxide inhibits antidiuretic hormone-stimulated osmotic water permeability in the collecting duct; however, the mechanism by which this occurs is unknown. We hypothesized that inhibition of antidiuretic hormone-stimulated water permeability by nitric oxide in the collecting duct is the result of activation of cGMP-dependent protein kinase, which in turn decreases intracellular cAMP. To test this hypothesis, we microperfused cortical collecting ducts. Antidiuretic hormone-stimulated water permeability was 317 +/- 47 microm/s (P < .001). Addition of spermine NONOate, a nitric oxide donor, to the bath decreased water permeability to 74 +/- 38 microm/s (P < .002). In the presence of LY 83583, an inhibitor of soluble guanylate cyclase, spermine NONOate did not change water permeability. Addition of spermine NONOate increased cGMP production (P < .01). In the presence of the cGMP-dependent protein kinase inhibitor, spermine NONOate did not change water permeability. Since antidiuretic hormone increases water permeability by increasing cAMP, we hypothesized that nitric oxide inhibits water permeability by decreasing cAMP. In tubules pretreated with antidiuretic hormone, intracellular cAMP was 18.9 +/- 3.9 fmol/mm. In tubules treated with antidiuretic hormone and spermine NONOate, cAMP was 9.3 +/- 1.7 fmol/mm (P < .03). We also examined the effect of spermine NONOate on dibutyryl-cAMP-stimulated water permeability. In the presence of dibutyryl-cAMP, water permeability was 388 +/- 30 microm/s. Addition of spermine NONOate had no significant effect on water permeability. Time controls and inhibitors by themselves did not change antidiuretic hormone-stimulated water permeability. We concluded that nitric oxide decreases antidiuretic hormone-stimulated water permeability by increasing cGMP via soluble guanylate cyclase, activating cGMP-dependent protein kinase and decreasing cAMP.
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PMID:Mechanism of the nitric oxide-induced blockade of collecting duct water permeability. 861 24

The effects of natriuretic peptides on electrical activity and cellular cGMP levels were studied in neurons of the supraoptic nucleus (SON) of rat hypothalamic slice preparations. Intracellular and extracellular recordings showed that bath application of A type natriuretic peptide (ANP) at 100 nM or B type natriuretic peptide (BNP) at 100 to 300 nM decreased the firing rate and hyperpolarized the membrane potential in phasically firing (putative vasopressin) neurons. Non-phasically firing (putative oxytocin) neurons did not respond to these natriuretic peptides in firing rate or membrane potential. The membrane-permeable cGMP analogue 8-bromo cGMP at 0.5 mM and the phosphodiesterase inhibitor 3/isobutyl-1-methylxanthine (IBMX) at 50 microM mimicked the inhibitory effects of ANP and BNP. The specific inhibitor of cGMP phosphodiesterase 1-(3-chloroanilino)-4-phenylphthalazine+ ++ (MY5445) at 30 microM also decreased the firing rate of SON neurons. The cGMP-dependent protein kinase inhibitor N-(2-(methylamino)ethyl)-5-isoquinoline-sulfonamide dihydrochloride (H8) at 1 microM abolished the inhibition by natriuretic peptides. We measured cGMP and cAMP contents in discrete SON regions and compared the change of contents before and after application of ANP and BNP. The increases in cellular cGMP accumulation were 430% for ANP and 120% for BNP, although they did not cause significant change of cAMP accumulation. The results suggest that the inhibitory effects of natriuretic peptides on putative vasopressin neurons are mediated through cGMP and cGMP-dependent protein kinase.
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PMID:Inhibitory effects of natriuretic peptides on vasopressin neurons mediated through cGMP and cGMP-dependent protein kinase in vitro. 868 Apr 19

In collecting duct principal cells, aquaporin 2 (AQP2) is shuttled from intracellular vesicles to the plasma membrane upon vasopressin (VP) stimulation. VP activates adenylyl cyclase, increases intracellular cAMP, activating protein kinase A (PKA) to phosphorylate AQP2 on the COOH-terminal residue, serine 256. Using rat kidney slices and LLC-PK1 cells stably expressing AQP2 (LLC-AQP2 cells), we now show that AQP2 trafficking can be stimulated by cAMP-independent pathways. In these systems, the nitric oxide (NO) donors sodium nitroprusside (SNP) and NONOate and the NO synthase substrate L-arginine mimicked the effect of VP, stimulating relocation of AQP2 from cytoplasmic vesicles to the plasma membrane. Unlike VP, these other agents did not increase intracellular cAMP. However, SNP increased intracellular cGMP, and exogenous cGMP stimulated AQP2-membrane insertion. Atrial natriuretic factor, which signals via cGMP, also stimulated AQP2 translocation. The VP and SNP effects were blocked by the kinase inhibitor H89. SNP did not stimulate membrane insertion of AQP2 in LLC-PK1 cells expressing the phosphorylation-deficient mutant 256SerAla-AQP2, indicating that phosphorylation of Ser256 is required for signaling. Both PKA and cGMP-dependent protein kinase G phosphorylated AQP2 on this COOH-terminal residue in vitro. These results demonstrate a novel, cAMP-independent and cGMP-dependent pathway for AQP2 membrane insertion in renal epithelial cells.
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PMID:Nitric oxide and atrial natriuretic factor stimulate cGMP-dependent membrane insertion of aquaporin 2 in renal epithelial cells. 1106 64

Natriuretic peptides bind their cognate cell surface guanylyl cyclase receptors and elevate intracellular cGMP concentrations. In vascular smooth muscle cells, this results in the activation of the type I cGMP-dependent protein kinase and vasorelaxation. In contrast, pressor hormones like arginine-vasopressin, angiotensin II, and endothelin bind serpentine receptors that interact with G(q) and activate phospholipase Cbeta. The products of this enzyme, diacylglycerol and inositol trisphosphate, activate the conventional and novel forms of protein kinase C (PKC) and elevate intracellular calcium concentrations, respectively. The latter response results in vasoconstriction, which opposes the actions of natriuretic peptides. Previous reports have shown that pressor hormones inhibit natriuretic peptide receptors NPR-A or NPR-B in a variety of different cell types. Although the mechanism for this inhibition remains unknown, it has been universally accepted that PKC is an obligatory component of this pathway primarily because pharmacologic activators of PKC mimic the inhibitory effects of these hormones. Here, we show that in A10 vascular smooth muscle cells, neither chronic PKC down-regulation nor specific PKC inhibitors block the AVP-dependent desensitization of NPR-B even though both processes block PKC-dependent desensitization. In contrast, the cell-permeable calcium chelator, BAPTA-AM (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetraacetoxymethyl ester), abrogates the AVP-dependent desensitization of NPR-B, and ionomycin, a calcium ionophore, mimics the AVP effect. These data show that the inositol trisphosphate/calcium arm of the phospholipase C pathway mediates the desensitization of a natriuretic peptide receptor in A10 cells. In addition, we report that CNP attenuates AVP-dependent elevations in intracellular calcium concentrations. Together, these data reveal a dominant role for intracellular calcium in the reciprocal regulation of these two important vasoactive signaling systems.
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PMID:Vasopressin-dependent inhibition of the C-type natriuretic peptide receptor, NPR-B/GC-B, requires elevated intracellular calcium concentrations. 1219 32

The suprachiasmatic nucleus (SCN) contains the primary mammalian circadian clock. This clock is entrained to environmental rhythms by external stimuli called zeitgebers. This entrainment is accomplished by the activation of specific, interacting signal transduction cascades. Since a cyclic guanosine monophosphate-dependent mechanism play a crucial functional role for light entrainment in the late night and for transmission of cholinergic stimuli, we examined the expression of protein kinase (PKG) in the rat SCN by means of qualitative and semi-quantitative immunocytochemistry. Immunoreaction (IR) for the isozyme protein kinase G I (PKG I) was found in the dorsomedial part of the SCN considered as an important relay in the output pathways of the clock. Within the SCN, PKG-I IR was colocalized with arginine-vasopressin-IR. The intensities of the PKG-I-IR did not vary between day and night.
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PMID:Protein kinase G I immunoreaction is colocalized with arginine-vasopressin immunoreaction in the rat suprachiasmatic nucleus. 1243 86

The nitric oxide (NO)-cGMP pathway regulates vascular tone and blood pressure by mechanisms that are incompletely understood. RGS2, a GTPase-activating protein for Gqalpha that is critical for blood pressure homeostasis, has been suggested to serve as an effector of the NO-cGMP pathway that promotes vascular relaxation based on studies of aortic rings in vitro. To test this hypothesis and its relevance to blood pressure control, we determined whether RGS2 functions as an NO effector in smooth muscle of the resistance vasculature. We report that 1) the ability of the NO donor sodium nitroprusside to reduce blood pressure is impaired in RGS2-/- mice, 2) vasopressin-triggered Ca2+ transients are augmented in smooth muscle cells from resistance arteries of RGS2-/- mice, and 3) cGMP analogs fail to inhibit vasopressin-triggered Ca2+ transients in smooth muscle cells from resistance arteries of RGS2-/- mice even though cGMP-dependent protein kinase (PKG)1alpha and PKG1beta are expressed and activated normally. These results indicated that the NO-cGMP pathway uses RGS2 as a novel downstream effector to promote vascular relaxation by attenuating vasoconstrictor-triggered Ca2+ signaling in vascular smooth muscle cells. Genetic or epigenetic impairment of this mechanism may contribute to the development of hypertension, and augmenting it pharmacologically may provide a novel means of treating this disease.
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PMID:RGS2 is a mediator of nitric oxide action on blood pressure and vasoconstrictor signaling. 1556 83

The rate of urine secretion by insect Malpighian tubules (MTs) is regulated by multiple diuretic and antidiuretic hormones, often working either synergistically or antagonistically. In the Drosophila melanogaster MT, only diuretic factors have been reported. Two such agents are the biogenic amine tyramine (TA) and the peptide drosokinin (DK), both of which act on the stellate cells of the tubule to increase transepithelial chloride conductance. In the current study, TA and DK signaling was quantified by microelectrode recording of the transepithelial potential in isolated Drosophila MTs. Treatment of tubules with cGMP caused a significant reduction in the depolarizing responses to both TA and DK, while cAMP had no effect on these responses. To determine whether a specific cGMP-dependent protein kinase (PKG) was mediating this inhibition, PKG expression was knocked down by RNAi in either the principal cells or the stellate cells. Knockdown of Pkg21D in the stellate cells eliminated the modulation of TA and DK signaling. Knockdown of Pkg21D with a second RNAi construct also reduced the modulation of TA signaling. In contrast, knockdown of the expression of foraging or CG4839, which encodes a known and a putative PKG, respectively, had no effect. These data indicate that cGMP, acting through the Pkg21D gene product in the stellate cells, can inhibit signaling by the diuretic agents TA and DK. This represents a novel function for cGMP and PKG in the Drosophila MT and suggests the existence of an antidiuretic hormone in Drosophila.
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PMID:Inhibition of diuretic stimulation of an insect secretory epithelium by a cGMP-dependent protein kinase. 2344 19