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 effects of urea structural analogues on the urea-facilitated diffusion system were examined in human red cell membranes (pink ghosts) and in antidiuretic hormone(ADH)-stimulated frog urinary bladder epithelia. In both tissues, urea permeability (P(urea)) was dramatically but reversibly inhibited by a number of urea analogues, such as 1-(3,4-dichlorophenyl)-2-thiourea (DCPTU). This urea derivative reduced the urea flux in a dose-dependent manner (90% inhibition of P(urea) at 0.5 mM concentration of DCPTU). With the aim of obtaining irreversible markers of red cell and urinary bladder urea transport systems, urea derivatives were modified by addition of an azido residue (N3) and preliminary experiments of photoaffinity labelling were carried out. Two synthetic urea derivatives: 1-(3-azido-4-chlorophenyl)-2-thiourea (ACPTU) and 1-(3-azido-4-chlorophenyl)-3-methyl-2-thiourea (Me-ACPTU) were shown to be very potent inhibitors of P(urea) when used in the absence of light, with IC50 values 60.3 microM and 31.6 microM respectively, as measured in frog urinary bladder. Both these molecules appeared to bind covalently to the urea carrier in both frog urinary bladder and human pink red cell ghosts, when illuminated in the presence of the tissue: the urea flux, which fell to 30-70% of the value obtained in the presence of ADH after inhibitor addition, remained low after the preparation had been illuminated for 30 min and the inhibitor removed. These results provide an interesting approach to the urea carrier analysis, particularly to the urea or urea analogue binding site on the transport protein.
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PMID:Urea derivatives as tools for studying the urea-facilitated transport system. 848 92

When toadfish are made ureotelic by a crowding/confinement protocol, they excrete approximately 90 % of their urea nitrogen (urea-N) production in large, irregular pulses (1-2 pulses per day) from the gill region. We investigated three hypotheses as to the mechanism of pulsatile excretion: (i) the presence of an active reabsorptive 'back-transport' mechanism that is periodically inhibited to allow urea-N excretion to occur; (ii) the periodic occurrence of a generalized, non-specific increase in gill permeability; and (iii) the presence of a specific facilitated diffusion transport system that is periodically activated. Exposure of toadfish during non-pulse periods to treatments designed to block a 'back-transport' mechanism (Na+-free sea water or the urea analogues 30 mmol l-1 thiourea or 30 mmol l-1 acetamide in the external water) did not stimulate a leakage of urea-N, thereby opposing the first hypothesis. The second hypothesis was opposed by several results. Neither injection of the potent branchial vasodilator L-isoprenaline (10(-5) mol l-1) nor infusion of NH4Cl, the latter at levels known to stimulate urea-N efflux in perfused gills, had any effect on urea-N excretion. Furthermore, during natural pulse events, when the normally very low gill permeability to urea (3x10(-7) cm s-1) increased at least 35-fold, there was no accompanying increase in permeability to either 3H2O (1.5x10(-5) cm s-1) or the paracellular marker [14C]PEG-4000 (10(-8) cm s-1). However [14C]thiourea permeability (1.5x10(-7) cm s-1) increased approximately fivefold, in support of the third hypothesis. Furthermore, when 30 mmol l-1 urea was placed in the external water, a concentration (60 000 micromol-N l-1) approximately three times that of blood (20 000 micromol-N l-1), each efflux pulse event (measured with [14C]urea) was accompanied by a net uptake, such that blood urea-N levels rose rather than fell. A proportional 1:1 relationship between influx per unit external concentration and efflux per unit internal (i.e. plasma) concentration indicated a fully bidirectional transport system. The simultaneous presence of 60 mmol l-1 thiourea in the external water inhibited the influx component by 73 %, further supporting this conclusion. These data, together with recent molecular, morphological and endocrinological evidence, strongly suggest that pulsatile urea-N excretion is caused by the periodic activation of a facilitated urea transporter in the gills, similar to the vasopressin-regulated urea transporter in the mammalian kidney.
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PMID:Pulsatile urea excretion in gulf toadfish (Opsanus beta): evidence for activation of a specific facilitated diffusion transport system. 946 61

An attempt has been made to assess the validity of applying the frictional and viscous coefficients of bulk water to the movement of water and solutes through the urinary bladder of the toad. The temperature dependence of diffusion of THO, C(14)-urea, C(14)-thiourea, and net water transfer across the bladder was determined in the presence and absence of vasopressin. The activation energy for diffusion of THO was 9.8 kcal per mole in the absence of vasopressin and 4.1 kcal per mole with the hormone present. Activation energies simultaneously determined following vasopressin for diffusion and net transfers of water were similar, and in the same range as known activation energies for diffusion and viscous flow in water. Urea had activation energies for diffusion of 4.1 and 3.9 kcal per mole in the absence and presence of vasopressin, respectively. Thiourea had a high activation energy for diffusion of 6.3 kcal per mole, which was unchanged, 6.6 kcal per mole, following hormone. These findings suggest that in its rate-limiting permeability barrier, water is present in a structured state, offering a high resistance to penetration by water. Vasopressin enlarges the aqueous channels so that the core of water they contain possesses the physical properties of ordinary bulk water. Urea penetrates the tissue via these aqueous channels while thiourea is limited by some other permeability barrier.
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PMID:The state of water in the isolated toad bladder in the presence and absence of vasopressin. 1390 90

Measurements have been made of the permeability of the isolated urinary bladder of the toad to a number of small solute molecules, in the presence and absence of vasopressin. Vasopressin has a strikingly specific effect on increasing permeability of the bladder to a group of small, uncharged amides and alcohols while penetration by other small molecules and ions is unaffected. The movement of urea is passive, as indicated by equal flux rates in the two directions. The reflection coefficients for chloride and thiourea indicate a high degree of impermeability of the bladder to these solutes even in the presence of large net movements of water. The low concentration of thiourea in the tissue water when this compound is added to the mucosal bathing medium indicates that the major permeability barrier to thiourea is at the mucosal surface of the bladder. The findings can be accounted for by a double permeability barrier consisting of a fine selective diffusion barrier and a porous barrier in series. The former would constitute the permeability barrier to most small solutes while the latter would be the rate-limiting barrier for water and the amides. It would be the porous barrier which is affected by vasopressin. Reasons are presented which require both barriers to be contained in or near the plasma membrane at the mucosal surface of the bladder.
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PMID:Permeability of the isolated toad bladder to solutes and its modification by vasopressin. 1446 23


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