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)

Studies on adenylate cyclase response of the nephron fragments to hormones and drugs have suggested that there is a functionally distinct segment tentatively called the connecting tubule (CNT), which is located between the distal (DT) and the cortical collecting tubule (CCT). The functional significance of these biochemical findings was examined with isolated rabbit renal tubules perfused in vitro. The transepithelial voltage (PDt) of the DT, CNT, and CCT were, respectively, -28.7 +/- 3.24 mV (24), -27.0 +/- 2.69 mV (24), and -3.5 +/- 2.14 mV (11) in the normal rabbits. The PDt of the CCT increased to -32.2 +/- 2.02 mV (33) when rabbits were pretreated for at least 3 days with deoxycorticosterone acetate, DOCA (1 mg/kg/day, i.m.), whereas the PDt of the DT and the CNT remained unchanged. The PDt of the CCT obtained from deoxycorticosterone acetate- (DOCA) treated animals decreased after addition of antidiuretic hormone (ADH) or isoproterenol (ISO) to the bath. The PDt of the CNT also responded to these agents, but the dose required to obtain the same response was quite different: The CNT was 100-fold more sensitive to ISO as compared to the CCT, whereas the CCT was 10-fold more sensitive to ADH than was the CNT. In contrast, the PDt of the DT did not respond to any of these agents, even at a higher concentration. After addition of ADH (200 microU/ml) to the bath, the osmotic water permeability (10(-8) cm2 . sec-1 . atm-1) of the CCT increased from 1.13 +/- 0.83 to 7.46 +/- 2.36, but that of the CNT remained low (0.36 +/- 0.78 in control vs. 0.48 + 0.64 after ADH). These observations support the view that the CNT is functionally distinct from either the DT or the CCT.
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PMID:The connecting tubule: a functional subdivision of the rabbit distal nephron segments. 51 94

The renal reabsorption of water independent of solute is the result of the coordinated function of the collecting duct and the ascending limb of the loop of Henle. The unique juxtaposition of the ascending and descending portions of the loop of Henle and of the vasa recta permits the function of a counter-current multiplier system in which water is removed from the tubular lumen and reabsorbed into the circulation. The driving force for reabsorption is the osmotic gradient in the renal medulla which is dependent, in part, on chloride (followed by sodium) pumping from the thick ascending loop of Henle. Urea trapping is also thought to play an important role in the generation of a hypertonic medullary interstitium. Arginine vasopressin (AVP) acts by binding to receptors on the cell membrane and activating adenylate cyclase. This, inturn, results in the intracellular accumulation of cyclic adenosine monophosphate (AMP) which in some fashion abruptly increases the water permeability of the luminal membrane of cells in the collecting duct. As a consequence, water flows along an osmotic gradient out of the tubular lumen into the medullary interstitium. Diabetes insipidus is the clinical condition associated with either a deficiency of or a resistance to AVP. Central diabetes insipidus is due to diminished release of AVP following damage to either the neurosecretory nuclei or the pituitary stalk. Possible causes include idiopathic, familial, trauma, tumor, infection or vascular lesions. Patients present with polyuria, usually beginning over a period of a few days. The diagnosis is made by showing that urinary concentration is impaired after water restriction but that there is a good response to exogenous vasopressin therapy. Nephrogenic diabetes insipidus can be identified by a patient's lack of response to AVP. Nephrogenic diabetes insipidus is caused by a familial defect, although milder forms can be acquired as a result of various forms of renal disease. Central diabetes insipidus is eminently responsive to replacement therapy, particularly with dDAVP, a long lasting analogue of AVP. Nephrogenic diabetes insipidus is best treated with a combination of thiazide diuretics as well as a diet low in sodium and protein.
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PMID:The clinical physiology of water metabolism. Part II: Renal mechanisms for urinary concentration; diabetes insipidus. 54 67

The reversibility of adenylate cyclase activation induced by vasopressin was studied by reducing the concentration of active peptide in contact with kidney medullo-papillary membranes. Reversibility of hormonal activation was only partial. The use of antagonists failed to demonstrate the reversibility of an adenylate cyclase activation induced by high affinity agonists. When antagonist was added after the agonist to membranes, a non-competitive inhibition was apparent. Active peptide was also eliminated from the incubation medium by treatment with agents capable of reducing the disulfide bridge of the hormonal molecule. Direct effects of reducers on adenylate cyclase activity were measured on enzyme activation induced by peptides lacking a disulfide bridge. There was no apparent correlation between the abilities of different reducers to inactivate free peptide in solution and their abilities to promote the reversibility of hormone-induced enzyme activation. Upon the addition of dithiothreitol, enzyme activity could be lowered to basal value and adenylate cyclase was again fully stimulatable. However, when dithiothreitol addition to stiumlated enzyme was combined with a 60-fold dilution of the incubation medium, no reversibility of hormonal activation occurred. These results illustrate that the processes involved in adenylate cyclase activation are only partially reversible.
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PMID:Vasopressin-sensitive adenylate cyclase. Reversibility of hormonal activation. 54 52

Newborns show an inability to concentrate maximally their urine. The vasopressin responsiveness of adenylate cyclase was, therefore, examined in membranes obtained from kidneys of neonatal and adult rats and from renal medulla and isolated collecting tubules of newborn and adult rabbits. In spite of higher basal and NaF-stimulated activity, vasopressin failed to stimulate adenylate cyclase from neonatal rat kidneys. In neonatal and adult rabbits, basal and NaF-stimulated adenylate cyclase activities of renal medullary membranes were comparable but vasopressin stimulation was significantly lower in the newborns. No change in hormonal activation constant was observed. This hyporesponsiveness of neonatal adenylate cyclase to vasopressin was confirmed with single isolated rabbit collecting tubules for adenylate cyclase determination, a highly sensitive preparation. It is intriguing to speculate that the low vasopressin stimulation of the medullary adenylate cyclase in the developing kidney may contribute to the known limitations of the urinary concentrating mechanism in the newborn period.
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PMID:Vasopressin responsiveness of renal adenylate cyclase in newborn rats and rabbits. 62 60

A "random-hit" matrix model is proposed to account for the dynamic and steady state relationship between occupation of bovine renal medullary membrane receptors by [Lys8]vasopressin (LVP) and neurohypophyseal hormones (NHH) and the associated activation of membrane-bound adenylate cyclase. The model was developed by systematic introduction of specific rules concerning receptor coupling into a general structural model which consists of two square matrices of identical size, one composed of homogeneous R ("receptor") units, the second of homogeneous C ("cyclase") units. R units are either occupied (RO) or unoccupied (RU); C units are either active (CA) or inactive (CI). Hormone molecules are envisioned to "collide" with R units randomly; collision with RU leads to "binding", and occupation is maintained for a characteristic mean occupancy time, TO. In this structure, each R unit has an "interaction field" which consists of the "twin" unit in the "C" matrix, and the 4 nearest neighbor C units surrounding the twin. Occupation of an R unit leads to activation of all CI units in the interaction field of that R; CA units in the interaction field are refractory. Thus binding at a given R may "recruit" a variable number of inactive neighboring C units (5, 4, 3, 2, 1, or 0). The model requires that there be individual coupling delays between the moment of binding at a given R and subsequent activation of CI units (mean coupling delay (Td) approximately 10% To). Activation of C units persists as long as the "parent" R is occupied and is maintained for an additional short time interval (Tp) after RO reverts to RU, corresponding to hormone dissociation from receptor. The model accounts for the following previously demonstrated relations between LVP occupation of receptors and adenylate cyclase activation in bovine renal medullary membranes: 1) the shape of the nonlinear steady state relation between normalized (percentage maximal) receptor occupation (O) and cyclase activation (A), uniformly observed in different membrane preparations: 2) variable hormone concentration-dependent trajectories of approach to the final steady state A:O value (A:Oss) which may be either monophasic or biphasic; 3) the loss of intrinsic adenylate cyclase activity observed in bovine membranes for a series of NHH analogs with progressively diminishing affinity for receptors. The model represents an explicit theory of coupling where a successive series of temporal events are quantitatively related to each other and privide major constraints to any interpretation of the molecular organization of receptors and adenylate cyclase units in membranes. The model excludes a number of mechanistic proposals and suggests a new hypothesis for membrane coupling with features which may be generally applicable to other hormone-sensitive adenylate cyclase systems.
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PMID:Neurohypophyseal hormone-responsive renal adenylate cyclase. IV. A random-hit matrix model for coupline in a hormone-sensitive adenylate cyclase system. 64 Oct 67

Cholera toxin, stereotaxically injected into the medial septal nucleus of the rat, leads within 24 h to a dramatic decrease in body weight and an increase in septal adenylate cyclase activity. Toxin-treated rats drink one-third the water of vehicle-treated animals while excreting two-and-one half times the urine. Food intake over the 24-h period is depressed to 13% of control but feces production was normal. The dramatic increase of urinary output suggests that cholera toxin activates a septal adenylate cyclase system which supressess the release of antidiuretic hormone. Cholera toxin injection into the septum may be a unique alternative to electrical stimulation for investigating septal involvement in the regulation of neuronal and metabolic processes.
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PMID:Increased adenylate cyclase activity and rapid weight loss following intraseptal injection of cholera toxin. 69 80

This study demostrates the existence of an adenylate cyclase sensitive to vasopressin in the medullary portion of the rat thick ascending limb. Maximal adenylate cyclase stimulations achieved in that segment (31-fold) were higher than those obtained in collecting tubules from the same rats (22-fold). From comparisons of absolute maximal responses it can be calculated that thick ascending limbs account for about 80% of the response to vasopressin of a kidney medulla homogenate. The apparent Km value of adenylate cyclase activation (from 10(-9)-2 x 10(-8) M) in thick ascending limbs was higher in each experiment than that simultaneously measured in the collecting tubules from the same rats (2 x 10(-10)-3 x 10(-9) M). Such a lower sensitivity is probably not due to a greater hormone degradation by the thick ascending limb samples. Experiments using structural analogues of the oxytocin series ([deamino-6-carba]oxytocin and vasotocin) did not give evidence for different vasopressin receptors in the thick ascending limb and the collecting tubule. A step beyond the hormone-receptor interaction, thus, must account for the different patterns of adenylate cyclase response to vasopressin of these two segments.
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PMID:Vasopressin-dependent adenylate cyclase activities in the rat kidney medulla: evidence for two separate sites of action. 74 23

Prolactin was shown to activate adenylate cyclase in broken cellular enzyme preparations from rat renal medulla. Likewise, vasopresin was effective on this enzyme system. Parathyroid hormone was similarly active in the renal cortex. The simultaneous administration of vasopressin and prolactin to medullary kidney slices did not result in an additive effect in stimulating medullary adenyl cyclase. Audioradiographic techniques revealed a selective and prolonged localization of intravenously injected 125I-prolactin to the thick limb of the loop of Henle, the distal tubule and the collecting duct. It is concluded that prolactin activates medullary adenylate cyclase, and may do so by occupying ADH receptors.
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PMID:Prolactin-induced stimulation of rat renal adenylate cyclase and autoradiographic localization to the distal nephron. 86 55

Rabbit distal convoluted tubules (DCT) microdissected from collagenase-treated kidneys were observed to contain up to four portions of a different appearance under stereomicroscopic examination: (1) a DCTa portion (generally very short), located right after the macula densa (MD) and resembling the portion of the limb (CAL) located before the MD; (2) a constant, "bright" portion, DCTb; (3) a constant, "granular" DCTg portion which, in most DCT, is connected to a portion of the collecting tubule of a similar "granular" appearance (CCTg); (4) many DCT having contacts with the kidney capsule in the superficial cortex were observed to contain an additional portion of a "light" appearance, DCTl, resembling the portion of the collecting tubule (CCTl) to which these superficial DCT are always branched. The hormone-dependent adenylate cyclase (AC) contained in these different portions was investigated by sectioning microdissected distal structures into successive samples according to the above-mentioned criteria, and by measuring with the help of a previously described micromethod, the enzyme activity contained in each single sample under one of the following conditions: control, parathyroid hormone. (PTH l U/ml), vasopressin, (AVP 10(-6)M), isoproterenol (10(-6)M), fluoride (5 X 10(-3)M). Highly significant and reproducible AC stimulations by these hormones were obtained for the following portions, respectively: DCTa, DCTg and CCTg with PTH; DCTl and CCTl with AVP; DCTg, CCTg and CCTl with isoproterenol. From these data, it is concluded that (a) the distal convoluted tubule can no longer be regarded as a single well-defined functional structure; (b) DCTa is actually a short CAL portion extending beyond MD, (c) DCTg and CCTg are two portions of a same functional segment; (d) similarly, DCTl belongs to the functional segment mainly constituted by CCTl; and, finally, (e) DCTb is the only functional segment which is entirely located in the distal convoluted tubule, i.e., included between the macula densa and the first branching with another tubule.
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PMID:Functional segmentation of the rabbit distal tubule by microdetermination of hormone-dependent adenylate cyclase activity. 94 Feb 69

1. Fatty acid synthesis, measured in the perfused liver of genetically obese (ob/ob) mice with 3H2O or [14C]actate, did not show the inhibition by [8-arginine]vasopressin (antidiuretic hormone) that is observed in livers from normal mice. 2. Hepatic glycogen breakdown in obese mice was stimuulated by vasopressin, but not as extensively as in lean mice. 3. If obese mice received a restricted amount of food, then fatty acid synthesis still did not respond to vasopressin, but glycogen breakdown was fully stimulated. 4. Cholesterol synthesis was not inhibited by vasopressin in livers from obese mice. 5. Vasopressin inhibited fatty acid synthesis in intact lean mice, but not in obese animals. 6. These results suggest that genetic obesity could be due to an inborn error within the mechanisms (other than adenylate cyclase) which mediate responses to extracellular effectors.
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PMID:Resistance to hepatic action of vasopressin in genetically obese (ob/ob) mice. 100 43


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