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)

Subcellular distribution of the enzymes related to the cellular action of antidiuretic hormone was studied in bovine renal medulla. The highest activity of vasopressin-stimulated adenylate cyclase was found in plasma membranes. The basal activity increased two times above homogenate while vasopressin-stimulated and NaF-stimulated activities both increased five times. Adenylate cyclase activity was present also in other particulate fractions, but it was not significantly stimulated by vasopressin. Cyclic AMP phosphodiesterase was predominantly located in the cytosol when assayed with 0.5 mM cyclic AMP or with 5 muM cyclic AMP. However, with the latter concentration of cyclic AMP more activity remained associated with the particulate fractions and was more inhibited by theophylline. The highest cyclic AMP-stimulated protein kinase activity occurred in the cytosol. Protein kinase activity present in other subcellular fractions was not markedly stimulated by cyclic AMP. Protein phosphatase activity was highest in cytosol when assayed using 32P-histones, 32P-plasma membrane proteins, and 32P-cytoslic proteins. The activity was unaffected by 10-6M to 10-4M cyclic AMP or cyclic GMP. The activity was completely inhibited by 10mM ZnSO4 and 10mM CuSO4; 10mM NaF inhibited the activity by approximately 14%. The enzymes related to the cellular action of vasopressin are predominatly localized in the cytosol except for the vasopressin-sensitive adenylate cyclase which is plasma membrane bound. To mediate the effect of antidiuretic hormone and act on the luminal plasma membrane these soluble enzymes and their substrates should be compartmentalized, possibly by a system of cytoplasmic microtubules.
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PMID:Subcellular distribution of the enzymes related to the cellular action of vasopressin in renal medulla. 16 75

Cyclic 3',5'-nucleotides play an important role in the action of neurohypophyseal hormones on peripheral tissues. All available evidence indicates that cyclic AMP serves as an intracellular mediator in the regulatory action of neurohypophyseal hormones on transport of fluids and solutes across both mammalian and nonmammalian epithelial membranes. There is a close association among binding of neurohypophyseal hormones on membrane, stimulation of cyclic AMP generation, and the functional response. On the other hand, neurohypophyseal hormones have no similar effect on cyclic AMP metabolism in contractile tissues such as smooth muscle. It appears likely that neurohypophyseal hormones stimulate primarily generation of cyclic GMP in contractile tissues, and the increase in cyclic GMP levels may be associated with the contractile response. While the role of cyclic AMP in neurohypophyseal hormone effects in epithelia is firmly established, the possible role of cyclic GMP in contractile responses is largely hypothetical at the present time.
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PMID:Cyclic nucleotides in the cellular action of neurohypophyseal hormones. 19 2

1. The central ganglia of a number of gastropod molluscs (including the marine snail Aplysia californica and the terrestrial snail Helix pomatia) contain neurones which exhibit endogenous patterns of oscillatory activity. 2. This oscillatory activity can be modulated for long periods of time by synaptic and hormonal stimulation. 3. Stimulation of appropriate pre-synaptic nerves causes long-lasting hyperpolarization in these neurones, with complete abolition of oscillatory activity. This synaptic response is mediated by an increase in K+ conductance, together with a decrease in inward (Na+/Ca2+) conductance. The ionic conductances affected by synaptic stimulation are those responsible for producing the rhythmic oscillations. 4. The oscillatory activity can also be modulated by the vertebrate neurohyophyseal peptides, vasopressin and oxytocin, and by an endogenous peptide-containing extract of molluscan ganglia. In contrast to synaptic stimulation, these agents cause an increase in oscillatory activity. 5. The endogenous molluscan factor which produces an increase in oscillatory activity can be purified by affinity chromatography on bovine neurophysin linked to Sepharose. This indicates that the molluscan nervous system may contain a neurohypophyseal-like peptide. 6. Oscillatory activity can be modulated by manipulation of cyclic nucleotide metabolism in these neurones. Increases in cAMP alone are associated with abolition of oscillatory activity; this mimics long-lasting synaptic hyperpolarization. Increases in cAMP and cGMP together are associated with an increase in oscillatory activity and mimic the effects of the vertebrate and molluscan peptides. Thus, it is possible that cyclic nucleotides play a role in these physiological responses.
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PMID:Synaptic and hormonal modulation of a neuronal oscillator: a search for molecular mechanisms. 51 75

The diverse biological actions of endothelins (ET) appear to be mediated by specific cell-surface receptors. Autoradiography and membrane binding studies have shown abundant ET binding sites in the kidney. However, their expression in specific types of renal cells is unclear. We studied the binding of 125I-labelled endothelin-1 in freshly isolated cell suspensions from canine inner medullary collecting duct. Competition binding experiments revealed the presence of specific high-affinity binding sites: unlabelled ET-1 and ET-2 compared with the radioligand with an IC50 of 135 and 83 pM, respectively, while the IC50 of ET-3 and big ET-1 were 2 and 4 orders of magnitude higher, indicating the presence of ETA-type receptor. Angiotensin II, vasopressin, and atrial natriuretic peptide (ANP) did not compete for ET binding even at a concentration of 10(-6) M. Saturation binding experiments showed a single class of binding sites of high density (Bmax = 56.7 +/- 10.3 fmol/10(6) cells) and high affinity (Kd = 69.8 +/- 10 pM). In contrast, ANP receptors in the same cell preparations appeared as two classes of binding sites with widely different affinity and density. The high-affinity ANP site (Kd = 311 +/- 48 pM) was compatible with ANP-B (guanylate cyclase-coupled) receptor. ET-1 did not compete for this receptor. ET-1 (10(-7) M) did not alter ANP-induced cGMP generation in these cells (3.8-fold increase at 10(-7) M ANP), nor basal levels of cGMP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specific endothelin binding sites in renal medullary collecting duct cells: lack of interaction with ANP binding and cGMP signalling. 128 83

Atrial stretch causes the release of atriopeptin (AP, ANF) from preformed vesicular storage sites. The circulating hormone acts on unique receptor sites (containing guanylate cyclase) to release guanosine 3',5'-cyclic monophosphate (cGMP) that mediates the natriuresis and vasodilation and probably the suppression of renin, aldosterone, and vasopressin. The biological effects of atriopeptin are transient because of the rapid inactivation of the circulating hormone (by neutral endopeptidase or clearance receptors) or the second messenger (by cGMP-phosphodiesterase). Heart failure due to chronic cardiac volume overload [aortovenocaval (A-V) fistula] exhibits markedly elevated circulating AP blood levels and urinary cGMP levels, accompanied by induction of ventricular AP gene and protein expression and release. Pharmacological manipulation of endogenous AP, either by inhibiting cGMP phosphodiesterase (i.e., mediator prolongation) or neutral endopeptidase (i.e., prolongation of hormone half-life) in A-V fistula animals results in profound natriuresis and diuresis without hypotension. These pharmacological maneuvers bypass the suppressed renal response to exogenous AP seen in heart failure and provide a rational therapeutic strategy based on our understanding of the underlying physiological and pathological mechanisms.
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PMID:Effect of pharmacological manipulation of endogenous atriopeptin activity on renal function. 131 20

We studied cyclic 3',5'-nucleotide phosphodiesterase (PDE) isozymes and their role in adenosine 3',5'-cyclic monophosphate (cAMP) and cGMP metabolism in a rat inner medullary collecting duct (IMCD) cell line. The homogenized and fractionated IMCD cells of cAMP-PDE and all of cGMP-PDE activity were found in the cytosol. The majority of cytosolic cAMP-PDE (greater than 50%) was isozyme PDE-IV; the Ca(2+)-calmodulin-sensitive PDE-I was present only in cytosol. Preincubation of IMCD cells with PDE-IV inhibitor rolipram markedly (5x) enhanced levels of cAMP both basal and in the presence of [Arg8]vasopressin (AVP). Cilostamide (for PDE-III) or vinpocetine had no effect, whereas PDE-I inhibitor 8-methoxymethyl-3-isobutyl-1-methylxanthine (8-MeoM-IBMX) enhanced AVP-dependent cAMP levels. Exposure of IMCD cells to 2 microM ionomycin decreased both basal and AVP-stimulated cAMP. Depletion of Ca2+ by preincubation of IMCD cells in the Ca(2+)-free medium with ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid markedly enhanced the stimulatory response of cAMP to AVP, and addition of 8-MeoM-IBMX further enhanced the AVP response. The levels of cGMP, basal or in response to atriopeptin (ANP), were not affected by PDE-V inhibitor zaprinast, but both inhibitors of PDE-I, 8-MeoM-IBMX and vinpocetine, increased basal cGMP, and 8-MeoM-IBMX also increased cGMP levels enhanced by ANP. The depletion of Ca2+ from IMCD cells alone had no effect on cGMP levels, but effects of 8-MeoM-IBMX and vinpocetine on the ANP-stimulated cGMP levels were enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclic 3',5'-nucleotide diesterases in dynamics of cAMP and cGMP in rat collecting duct cells. 132 Mar 33

The renin-angiotensin-aldosterone system is activated by diuretics and involved in the diuretic resistance of cirrhotic patients with ascites and oedema. In previous studies relatively high doses of captopril (25-400 mg daily) were unsuccessful in promoting diuresis and natriuresis in these patients. We analyzed the efficacy of a low dose of captopril in eight patients with massive ascites resistant to therapy of salt/fluid restriction and increasing doses of spironolactone and furosemide. Mean duration of diuretic use was 73 days (range 7-240 days). After at least 3 days of observation on 80 mg furosemide and 100 mg spironolactone only, captopril was added. Four out of eight patients responded with an increase in natriuresis and diuresis; daily dose of captopril was 20.6 mg in responders and 26.5 mg in non-responders. After the addition of captopril the mean weight change was -7.5 kg in responders and +0.25 kg in non-responders. Mean urinary sodium output in responders increased from 72.8 (S.D. = 35.2) to 128.5 (63.5) mmol within 10 days. Increased diuresis in responders made diuretic reduction necessary: mean furosemide from 80 to 53.3 mg, and mean spironolactone from 100 to 68.1 mg. Creatinine clearances remained stable. High levels of plasma renin activity, plasma aldosterone and angiotensin-II were found in all patients. Non-responders showed more severe hyponatremia and higher vasopressin levels. Natriuretic atrial factor (NAF) was in the upper-normal range or slightly elevated in both groups. In non-responders we noticed low levels of cGMP in 24-h urine, compared with responders.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Efficacy of low-dose captopril in addition to furosemide and spironolactone in patients with decompensated liver disease during blunted diuresis. 132 74

The distribution of binding sites for atrial natriuretic peptide (ANP) has been examined in frozen sections of the guinea pig inner ear by means of autoradiography. The highest density was found in the stria vascularis of all cochlear turns. In membrane preparations of stria vascularis in vitro, the production of the second messenger cGMP was strongly stimulated by synthetic ANP in a dose dependent manner. Adenylate cyclase was neither stimulated nor inhibited by ANP, thus suggesting, that the binding sites coincide with an ANP receptor, which is coupled to guanylate cyclase but not negatively coupled to an adenylate cyclase molecule. The production of cyclic GMP could not be reduced by GDP-beta S, a strong inhibitor of the Gs protein. We conclude the existence of an ANP receptor-guanylate cyclase signal transfer system, similar to the beta 2 receptor-adenylate cyclase system in the inner ear, without coupling to a G protein. ANP might play a role in sodium and water regulation of the endolymph and might antagonize the action of vasopressin.
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PMID:Binding sites of atrial natriuretic peptide (ANP) in the mammalian cochlea and stimulation of cyclic GMP synthesis. 133 79

Granulosa cells isolated from ovaries of non-cycling, cycling and pregnant rabbits of the same age were cultured in vitro either without or with pFSH (1 micrograms/ml), bLH (1 IU/ml), LH-RH (25 ng/ml) or arginine-8-vasotocin (100 ng/ml). The production of immunoreactive progesterone, estradiol-17 beta, oxytocin, arginine-8-vasopressin and cGMP was analyzed. The gonadotropins did not show any significant effects on the cells isolated from non-cycling and cycling rabbits, but not from these of pregnant ones. LH-RH inhibited and vasotocin stimulated progesterone production. All hormones used stimulated estradiol release from cells of non-cycling rabbits, while in a case of cycling animals no change was found. In the cell from pregnant females the release of estradiol was enhanced after LH treatment only. The treatment with FSH and LH (but not with LH-RH or vasotocin) resulted in a remarkable rise of granulosa vasopressin surge irrespectively to the reproductive stage. Oxytocin production by granulosa cells incubated either without or with LH, LH-RH or vasotocin was undetectable. However, FSH strongly stimulated oxytocin release. FSH and in lesser extent, LH or LH-RH (but not vasotocin) activated granulosa cGMP production in the cells from cycling and pregnant (but not from non-cycling) animals. It was also found that, in contrast to other reproductive stages, basal progesterone release from the cells of pregnant rabbits was increased, while in a case of non-cycling animals the basal estradiol release was decreased and that of cGMP was increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of FSH, LH, LH-RH and arginine-vasotocin on the production of steroids, nonapeptide hormones and cGMP by rabbits granulosa cells isolated at different stages of reproductive cycle. 133 99

Old concepts of an "inert" vascular endothelium have been entirely discredited. It is now known that the vascular endothelium and media form a "functional unit", communicating via both electric and humoral signals. Normal endothelium maintains vascular dilation through release of various dilatory substances, the main one being endothelial relaxing factor (EDRF), which is nitric oxide (NO). EDRF is, for example, released in response to increased shear stress that accompanies high flow rates, and acts by engaging the cyclic GMP system of smooth muscle cells. Even potential vasoconstrictors such as vasopressin, catecholamines and serotonin release EDRF. Endothelial release of prostacyclin supplements the EDRF action. EDRF (and prostacyclin) also inhibit platelet aggregation. In the presence of hypertension and/or atherosclerosis, endothelial function is often impaired and pressor/thrombogenic factors such as endothelin, thromboxane, vasopressin, catecholamines, and serotonin become more dominant. Antihypertensive therapy should, ideally, seek to restore endothelial function to normal.
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PMID:Hypertension and endothelial function--aspects of atheroma protection. 134 64


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