Published August 1, 1976
Nature of the Water Permeability Increase
Induced by Antidiuretic Hormone (ADH)
in Toad Urinary Bladder and Related Tissues
ALAN FINKELSTEIN
From the Departments of Physiology, Neuroscience, and Biophysics,
Albert Einstein College of Medicine, Bronx, New York 10461
INTRODUCTION
T h r e e criteria are traditionally cited as evidence for aqueous pores in cell
m e m b r a n e s or tissues: (a) ratios o f osmotic permeability coefficient (Pt) to tracer
permeability coefficient o f water (Pa(H20)) significantly greater than 1, (b)
solvent d r a g o f solutes a c c o m p a n y i n g osmotic flow, a n d (c) g r a d e d permeability
to small molecules (molecular sieving). Unstirred layers make it impossible to
establish the true existence o f . t h e first criterion in almost all cases, with the
possible exception o f the red cell (Dainty, 1963), and also c o m p r o m i s e the second
criterion (Hays, 1972). This leaves molecular sieving, which can convincingly
establish the existence o f p o r e s in some cases (e.g. Beggiatoa [Ruhland a n d
H o f f m a n n , 1925]), but not if the pores admit only water (or water a n d very small
solutes such as acetamide and urea). T h e water a n d nonelectrolyte permeability
o f lipid bilayers (Finkelstein, 1976), however, suggest a new criterion for deciding the path o f water m o v e m e n t , which I shall apply to the action o f antidiuretic
h o r m o n e (ADH).
Until recently, most physiologists believed that A D H caused an increase in the
THE JOURNAL OF GENERAL PHYSIOLOGY " VOLUME 6 8 ,
1976 ' p a g e s 1 3 7 - 1 4 3
137
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ABST RACT In artificial lipid bilayer membranes, the ratio of the water permeability coefficient (Pe (water)) to the permeability coefficient of an arbitrary nonelectrolyte such as n-butyramide (Pa(n-butyramide)) remains relatively constant with
changes in lipid composition and temperature, even though the individual Pe's
increase more than 100-fold. I propose that this is a general rule that also holds for
the lipid bilayers of cells and tissues, and that therefore if Pa(water)/Pa(solute)
greatly exceeds the value found for artificial lipid bilayers (where "solute" is a
molecule, such as 1,6 hexanediol or n-butyramide, that crosses the cell membrane
by a solubility-diffusion mechanism without the aid of a special transporting system), then water crosses the cell membrane via aqueous pores. Applying this
criterion to the toad urinary bladder, we find that even in the unstimulated
bladder, water probably crosses the luminal membrane primarily through small
aqueous pores, and that this is almost certainly the case after antidiuretic hormone
(ADH) stimulation. I suggest that ADH stimulation ultimately leads either to
formation (or enlargement) of pores, by the rearrangement of preexisting subunits, or to an unplugging of these pores.
Published August 1, 1976
|38
THE JOURNAL OF GENERAL PHYSIOLOGY • VOLUME 68 ' 1976
size o f aqueous pores in the o u t e r surface o f f r o g skin ( K o e f o e d - J o h n s e n a n d
Ussing, 1953) a n d the luminal (or mucosal) surface o f toad urinary b l a d d e r
(Hays a n d Leaf, 1962). T h a t belief rested on observed differences between Pt
a n d P d ( H 2 0 ) as well as solvent d r a g effects ( K o e f o e d - J o h n s e n a n d Ussing, 1953;
A n d e r s e n and Ussing, 1957; Hays a n d Leaf, 1962, L e a f a n d Hays, 1962). Since
those observations probably result f r o m artifacts o f unstirred layers (Hays,
1972), however, they do not s u p p o r t the theory that water crosses those tissues
t h r o u g h a q u e o u s pores. In fact, t h e r e is an e m e r g i n g view that water traverses
the luminal m e m b r a n e o f b l a d d e r a n d collecting tubules by a solubility-diffusion
m e c h a n i s m , a n d that A D H increases water permeability by increasing m e m b r a n e fluidity (Schafer et al., 1974; Pietras a n d Wright, 1975). T h e results o f the
previous p a p e r (Finkelstein, 1976) b e a r directly on this question, a n d , as we shall
see, a r g u e strongly for water crossing A D H - s t i m u l a t e d tissues t h r o u g h a q u e o u s
pores.I
THEORY
Application of the Theory to the Action of ADH on the Toad Urinary Bladder
REASONS
FOR
BELIEVING
THAT
WATER
GOES
THROUGH
PORES
IN THE
TOAD
BLAVDER Consider the n - b u t y r a m i d e a n d water permeabilities o f the sphingomyelin:cholesterol (SC) m e m b r a n e at 14.5°C (Table II, c o l u m n 3) c o m p a r e d to
those o f u n s t i m u l a t e d toad b l a d d e r mucosal m e m b r a n e (the limiting p e r m e a b i l ity barrier) (Table I I , c o l u m n 4). T h e n - b u t y r a m i d e permeabilities are essentially
the s a m e , thus indicating that the two bilayers are o f equal tightness. O n the
It is generally agreed that the chief barrier to water movement is the luminal (mucosal) surface of
the toad urinary bladder and mammalian collecting tubules, and that ADH acts by increasing its
permeability (Handler and Orloff, 1973). (In the fully stimulated bladder, the water permeability of
the luminal surface may be so large that other series barriers [e.g. the serosal membrane of the
epithelial cells] now offer significant resistance to water movement and hence help determine the
value ofPt. ) There remains the issue, however, of whether water moves across the luminal plasma
membrane of the epithelial cells or through the "tight" junctions between those cells. All evidence
favors the former (Civan and DiBona, 1974); in fact there is good evidence that ADH affects the
water permeability of the luminal plasma membrane of the granular cells (DiBona et al., 1969). We
shall therefore assume that the permeability barrier is the luminal plasma membrane of the single
layer of epithelial cells lining the lumen of the bladder and collecting tubules.
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T h e p e r t i n e n t observation f r o m bilayers is that Pd(water)/Pd(sOlute) r e m a i n s
relatively constant with changes in lipid composition a n d t e m p e r a t u r e , even
t h o u g h the Pd'S c h a n g e by as m u c h as a 100-fold (Finkelstein, 1976). I p r o p o s e
that this is a general rule that holds for all lipid bilayers. T h e r e f o r e , if water
traverses the lipid bilayer o f a cell or tissue primarily by a solubility-diffusion
m e c h a n i s m , Pa (water)/Pn (solute) should a p p r o x i m a t e the value f o u n d in artificial bilayers (for those solutes [such as 1,6 hexanediol, 1,4 butanediol, isobutyra m i d e , a n d n - b u t y r a m i d e ] that p e r m e a t e cell m e m b r a n e s without aid o f special
t r a n s p o r t i n g systems [see T a b l e I]). Conversely, if Pa(water)/Pd(sOlute) greatly
exceeds the c o r r e s p o n d i n g value in the first three rows o f T a b l e I, s t r o n g
evidence exists that water crosses the m e m b r a n e by an alternative m e c h a n i s m
(e.g. via pores).
Published August 1, 1976
A. FINKELSTEIN WaterPermeabilityIncrease Induced by ADH in Toad Bladder
139
o t h e r h a n d , Pa ( w a t e r ) o f u n s t i m u l a t e d t o a d b l a d d e r is six t i m e s l a r g e r t h a n t h a t
o f SC b i l a y e r at 14.5°C, s u g g e s t i n g t h a t e v e n in t h e a b s e n c e o f A D H , w a t e r m o v e s
through a path separate from that of butyramide. After maximal ADH stimulation o f t h e b l a d d e r , P a ( H z O ) i n c r e a s e s m o r e t h a n 15-fold to o v e r 2 × 10 -a c m / s
TABLE
I
R A T I O S O F Pa(H20) T O Pa(SOLUTE) FOR LIPID BILAYER MEMBRANES A N D
T O A D URINARY BLADDER
Membrane
Pd(H,O)/Pa(n-butyramide)
SC, 14.5°
SC, 25 °
LC, 25°
Unstimulated
bladder
Stimulated
bladder
P~(H,O)/Pe(isobutyramide) Pd(HIO)/P~(I,4 butanediol)
4.1
2.8
1.9
6.9
2.9
Pe(H20)/Pa(I,6 hexanediol
27
29
1.8
2.6
24
81
81
18
600
1,400
1,900
460
TABLE
II
COMPARISON O F T H E VALUES O F T H E P E R M E A B I L I T Y C O E F F I C I E N T S
(Pa's) O F W A T E R A N D N O N E L E C T R O L Y T E S FOR
S P H I N G O M Y E L I N : C H O L E S T E R O L (SC) MEMBRANES T O T H O S E FOR T O A D
URINARY BLADDER
10 ~ P~ (crn/s)
Molecule
SC, 25 °*
1,6 Hexanediol
n-Butyramide
Isobutyramide
1,4 Butanediol
450
288
118
30
H~O
Acetamide
Urea
810
21
<6.1 [I
SC, 14.5"*
51
210
Bladder~:,
(unstimulated)
Bladder§,
(stimulated)
P,~(unstim ulated
bladder)
Pal(stimulated
bladder)
P~(SC, 25°)
Pa(SC, 25°)
72
54
16
16
108
86
35
27
0.16
0.19
9.14
0.53
1,300
16
14
> 13,000
72
49
1.6
0.76
>2.3
0.24
0.30
0.30
0.90
> 16
3.4
>8
* Finkelstein, 1976 (SC stands for sphingomyelin:cholesterol bilayer).
:~ Wright and Pietras (1974).
§ Pietras and Wright (1975).
II 6.1 × 10-~ cm/s is the value for Pal(urea) on lecithin:cholesterol bilayers (Finkelstein, 1976).
( H a y s , 1972). T h e e x a c t v a l u e is i m m e a s u r a b l e b e c a u s e o f u n s t i r r e d l a y e r p r o b lems, but assuming for the moment that water traverses the bilayer by a solubili t y - d i f f u s i o n m e c h a n i s m , P a ( H 2 0 ) = P t ~ 5 × 10 -3 c m / s ( H a y s , 1972). O n t h e
o t h e r h a n d , P a ( n - b u t y r a m i d e ) i n c r e a s e s o n l y by 60% to 86 × 10 -7 c m / s ( P i e t r a s
a n d W r i g h t , 1975). T h u s , t h e ' A D H - t r e a t e d b l a d d e r h a s a n n - b u t y r a m i d e p e r m e a b i l i t y less t h a n twice t h a t o f t h e SC b i l a y e r at 14.5°C, b u t a w a t e r p e r m e a b i l i t y
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T h e figures for sphingomyelin:cholesterol membranes (SC) and lecithin:cholesterol membranes (LC) are calculated from the data in
Table 1 of the preceding p a p e r (Finkelstein, 1976). T h e figures for unstimulated and stimulated bladder are calculated from the data
in Table II o f this paper, where we have assumed that Pd = P/and that P t = 5 x 10-3 cm/s (Hays, 1972).
Published August 1, 1976
140
THE JOURNAL OF GENERAL PHYSIOLOGY • VOLUME 08 " 1976
m o r e t h a n 200 t i m e s t h a t o f t h e s a m e b i l a y e r . I n o t h e r w o r d s , Pa(H20)/Pa(nb u t y r a m i d e ) in t h e A D H - t r e a t e d b l a d d e r is m o r e t h a n 100-fold g r e a t e r t h a n in
t h e SC b i l a y e r at 14.5°C. 2 I b e l i e v e t h a t this is c o m p e l l i n g e v i d e n c e t h a t w a t e r
does not cross the mucosal surface of the ADH-stimulated bladder by a solubility-diffusion mechanism, but instead crosses through aqueous pores.
FURTHER
REASONS
FOR
REJECTING
A SOLUBILITY-DIFFUSION
MECHANISM
FOR
2 It is also more than 100-fold greater than in the SC bilayer at 25° or the LC bilayer at 25° (Table I,
column 2). I have focused on the SC bilayer at 14.5°, because its permeability to n-butyramide is so
close to that of the bladder that a comparison can be made of systems of equal "tightness." Even at
25°C, however, Pa values on SC membranes for 1,6 hexanediol, isobutyramide, and n-butyramide
are only about six times larger than those on unstimulated toad bladder (Table I I, column 6). (Pa(1,4
butanediol) is only 1.9 times larger. This may result from a spuriously high value of Pn(1,4
butanediol) on the unstimulated [and also on the stimulated] bladder, because of contamination of
[1,4-14C]butanediol with a few percent of a relatively lipophilic material [Finkelstein, 1976l.) The SC
bilayer at 25° is thus of comparable tightness to the bilayer of the bladder's mucosal membrane. Even
the discrimination between isobutyramide and n-butyramide by the SC bilayer is comparable to that
by the bladder. On the other hand, Pn(acetamide) of SC bilayer at 25° is about equal to that of the
unstimulated bladder and Pd(H,O) of SC bilayer at 25° is about one-half that of the bladder (Table
II, column 6). In other words, the unstimulated toad bladder is 5-10 times more permeable to
acetamide and water than might be expected from its permeability to the larger solutes. It is also
much more permeable to urea, even more so than is the "looser" LC bilayer. Thus, even in the nonADH-treated bladder, these small molecules (H~O, acetamide, and urea) may permeate primarily via
a separate pathway from that of the larger molecules.
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WATER TRANSPORT iN THE TOAD BLADDER P i e t r a s a n d W r i g h t (1974) f o u n d t h a t
t h e p e r m e a b i l i t i e s o f m o l e c u l e s t h a t p r e s u m a b l y c r o s s t h e m u c o s a l b i l a y e r by a
s o l u b i l i t y - d i f f u s i o n m e c h a n i s m (e.g. n i c o t i n a m i d e , b u t y r a m i d e , c a f f e i n e , a n d
h e x a n e d i o l ) i n c r e a s e modestly (at m o s t t w o f o l d ) u p o n A D H s t i m u l a t i o n , a n d
therefore concluded (rightly, I believe) that ADH stimulation increases the
fluidity of that bilayer. They further suggested, however, that the much larger
A D H - i n d u c e d i n c r e a s e s in w a t e r , u r e a , a n d a c e t a m i d e p e r m e a b i l i t i e s ( m o l e c u l e s
w h i c h t h e y call " h y d r o p h i l i c " as d i s t i n c t f r o m t h e o t h e r s w h i c h t h e y call " l i p o p h i l i c ' ) r e s u l t f r o m this s a m e m e c h a n i s m . T h e y state: "It is n o w r e c o g n i z e d t h a t
t h e p a r t i t i o n o f s o l u t e s i n t o b i o l o g i c a l a n d artificial m e m b r a n e s p r o b a b l y v a r i e s
w i t h p o s i t i o n in t h e m e m b r a n e ; l i p o p h i l i c s o l u t e s a r e e x p e c t e d to b e p a r t i t i o n e d
mainly into the hydrocarbon core of the membrane, whereas hydrophilic solutes
a r e p r o b a b l y l o c a t e d n e a r e r t h e p o l a r h e a d g r o u p s o f t h e l i p i d s . [ R e f e r e n c e to
D i a m o n d a n d K a t z , 1974.] C o n s e q u e n t l y , changes in fluidity of a membrane could
produce quantitatively different effects on lipophilic and hydrophilic solutes [ m y italics].
I f , f o r e x a m p l e , A D H c a u s e d a r e l a t i v e l y l a r g e r i n c r e a s e in t h e f l u i d i t y at t h e
p e r i p h e r y t h a n in t h e c o r e o f t h e b l a d d e r m e m b r a n e s , t h e r e s h o u l d be a g r e a t e r
i n c r e a s e in t h e p e r m e a b i l i t y o f h y d r o p h i l i c s o l u t e s t h a n l i p o p h i l i c s o l u t e s . "
T h i s s t a t e m e n t a c t u a l l y p r o m p t e d t h e p r e s e n t s t u d y ( F i n k e l s t e i n , 1976). O n
t h e o r e t i c a l g r o u n d s it is n o t r e a s o n a b l e . T h e p e r m e a b i l i t y b a r r i e r is t h e h y d r o c a r b o n c o r e o f t h e m e m b r a n e ; t h e r e f o r e , o n l y p a r t i t i o n i n g i n t o this r e g i o n is
r e l e v a n t , r e g a r d l e s s o f w h e t h e r a m o l e c u l e is h y d r o p h i l i c o r l i p o p h i l i c . B u t
t h e o r y a s i d e , I w a n t e d to see i f f l u i d i t y c h a n g e s in l i p i d b i l a y e r s c o u l d p r o d u c e
h u g e i n c r e a s e s in w a t e r p e r m e a b i l i t y with o n l y m o d e s t i n c r e a s e s in p e r m e a b i l i t y
for larger, more lipophilic molecules (e.g. butyramide).
Published August 1, 1976
A. FINKELSTEIN WaterPermeabilityIncreaseInducedby ADH in ToadBladder
141
Nature of ADH-Induced Pores
THE SlZ~ OF THE PORES T h e A D H - i n d u c e d p o r e s m u s t be very small (~2-/~
radius), a d m i t t i n g H 2 0 a n d possibly a c e t a m i d e a n d u r e a . 4 I n the cortical collecting tubules o f the k i d n e y , A D H increases only w a t e r p e r m e a b i l i t y ( G r a n t h a m a n d
B u r g , 1966); a p p a r e n t l y these p o r e s , at least, are too small to a c c o m m o d a t e
a c e t a m i d e a n d u r e a . (Lest o n e feel t h a t a p o r e t h r o u g h w h i c h only water c a n pass
strains the d e f i n i t i o n o f a p o r e , g r a m i c i d i n A, an u n a m b i g u o u s p o r e - f o r m e r in
lipid bilayers [ H l a d k y a n d H a y d o n , 1972], creates p o r e s t h a t a r e p e r m e a b l e to
water b u t not to u r e a [Finkelstein, 1973].) Since, P/Pal(H20) in such p o r e s is
p r o b a b l y n o t m u c h g r e a t e r t h a n 1,5 this criterion f o r p o r e s is n o t v e r y u s e f u l ,
e v e n if u n s t i r r e d layers w e r e n o t a p r o b l e m .
HOW M I G H T ADH STIMULATION LEAD TO PORE FORMATION?
The rapidity of
the A D H r e s p o n s e m a k e s it unlikely that de nov~ synthesis o f p o r e f o r m e r s
( p r o b a b l y proteins) o c c u r s . I p r o p o s e that the p o r e s (or their subunits) p r e e x i s t
in the l u m i n a l m e m b r a n e , b u t m o s t o f t h e m are n o t p a t e n t . T h e y m i g h t be
These were double-label experiments in which Pa's for THO and a 14C-solute were first measured
in the absence of phloretin, phloretin then added to the same membrane, and the subsequent Pa's
determined.
4 The ability of phloretin to inhibit ADH-induced urea and acetamide permeability without affecting
water permeability (Levine et al., 1973) suggests that the urea and acetamide permeability pathway is
separate from that of water. There is, however, an alternative possibility. Since Pd (HtO) in the AD Hstimulated bladder is several hundred-fold larger than Pa(urea) (Hays, 1972), the aqueous pore may
just barely admit urea. Therefore, if phioretin either slightly reduces the pore radius or slightly
obstructs the pore entrance, urea permeability would decline almost to zero without water permeability being affected. (Interestingly, there /s a 50% reduction in water permeability at maximal
phioretin concentrations [Levine et al., 1973].) The recent finding by Levine et al. (1976), however,
that at certain concentrations some general anesthetics inhibit water permeability without affecting
urea permeability, appears to favor independent pathways for urea and water transport.
s This can be argued theoretically (Manning, 1975) and from the observation that PAPa(H20) is only
3 for nystatin and amphotericin B pores, which admit nonelectrolytes up to the size of glucose (Holz
and Finkelstein, 1970).
3
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I f o u n d n o s u c h effect (Finkelstein, 1976); o n the c o n t r a r y , t h e r e was a small
t r e n d in the o p p o s i t e direction. W h e t h e r fluidity was i n c r e a s e d by r e m o v i n g
cholesterol ( g o i n g f r o m L C to L), c h a n g i n g the p h o s p h o l i p i d ( g o i n g f r o m SC to
LC), o r raising the t e m p e r a t u r e ( g o i n g f r o m SC [14.5 °] to SC [25°]), the increase
in Pd f o r the lipophilic solutes ( n - b u t y r a m i d e , i s o b u t y r a m i d e , 1,4 b u t a n e d i o l ,
a n d 1,6 h e x a n e d i o l ) a n d i n d e e d f o r the o t h e r h y d r o p h i l i c solutes ( f o r m a m i d e ,
a c e t a m i d e , a n d u r e a ) was (within e x p e r i m e n t a l e r r o r ) e i t h e r equal to o r slightly
g r e a t e r t h a n the increase in Pd (water), in striking c o n t r a s t to the action o f A D H
(see especially T a b l e I). E v e n the increase in p e r m e a b i l i t y p r o d u c e d by p h l o r e t i n
( p r o b a b l y by a fluidity c h a n g e ) was g e n e r a l l y smaller ( a n d n e v e r larger) f o r w a t e r
t h a n f o r the c o m p a n i o n solute tested, a T h u s , n e i t h e r physical t h e o r y n o r e x p e r i m e n t s with lipid bilayers o f f e r the slightest s u p p o r t to the n o t i o n that the l a r g e
A D H - i n d u c e d increases in the w a t e r p e r m e a b i l i t y o f t o a d b l a d d e r result f r o m a
g r e a t e r solubility a n d / o r d i f f u s i o n c o n s t a n t o f w a t e r in the m u c o s a l bilayer.
C o n s e q u e n t l y , I believe t h a t A D H stimulation ul~mately leads to the creation of
aqueous pores.
Published August 1, 1976
142
THE
JOURNAL OF GENERALPHYSIOLOGY" VOLUME68 " 1976
" p l u g g e d " by s o m e m o l e c u l e , o r the s u b u n i t s f o r m i n g the p o r e m a y be so
a r r a n g e d t h a t t h e o p e n i n g is e i t h e r n o n e x i s t e n t , o r too s m a l l to a d m i t water.
A D H t h e n leads (via cyclic A M P , etc. 6) to u n p l u g g i n g o f the p o r e , o r r e a r r a n g e m e n t o f t h e s u b u n i t s to f o r m a n o p e n i n g (or a l a r g e r o p e n i n g ) . P e r h a p s the
fluidity c h a n g e o b s e r v e d by Pietras a n d W r i g h t (1974) allows the s u b u n i t s to
f o r m a m o r e o p e n c o n f i g u r a t i o n , o r allows the j u n c t i o n o f " h a l f p o r e s " (located
in the i n n e r a n d o u t e r leaflets o f the l u m i n a l bilayer) to f o r m a c o m p l e t e , waterp e r m e a b l e p o r e ( C h e v a l i e r et al., 1976).
This work was supported by NSF grant no. BMS 74-01139.
Receivedfor publication 5 March 1976.
REFERENCES
6 The prevailing view is that ADH acts indirectly by stimulating an adenylcyclase, leading to increased
intracellular levels of 3',5' cyclic AMP and ultimately, through God knows how many steps, to
alteration of luminal membrane permeability (Handler and Orloff, 1973). The suggestions that ADH
acts directly on the luminal membrane (Graziani and Livne, 1971; Pietras and Wright, 1974) are not
persuasive.
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ANDERSEN, B., and H. H. USSING. 1957. Solvent drag on non-electrolytes d u r i n g osmotic
flow through isolated toad skin and its response to antidiuretic hormone. Acta Physiol.
Scand. $9"228-239.
CHEVALIER, J., ,1. BORGUET, and J. S. HUGON. 1976. Relation between permeability and
ultrastructure changes induced by antidiuretic hormone. Biophys. J. 16:7a.
CIVAN, M. M., and D. R. DI BONA. 1974. Pathways for movement of ions and water across
toad urinary bladder. I I. Site and mode of action of vasopressin.J. Membr. Biol. 19:195220.
DAm'r'v, J. 1963. Water relations of plant cells. Adv. Bot. Res. 1:279-326.
DIAMOND, J. M., and Y. KATZ. 1974. Interpretation of nonelectrolyte partition coefficients between dimyristol lecithin and water. J. Membr. Biol. 17:121-154.
DI BONA, D. R., M. M. CIVAN, and A. LEAr. 1969. The cellular specificity of the effect of
vasopressin on toad urinary bladder. J. Membr. Biol. 1:79-91.
FINKELSTEIN, A. 1973. Aqueous pores created in thin lipid membranes by the antibiotics
nystatin, amphotericin B and gramicidin A: implications for pores in plasma membranes. In Drugs and T r a n s p o r t Processes. B. A. Callingham, editor. MacMillan Press
Ltd., London. 241-250.
FINKELSTEIN, A. 1976. The water and nonelectrolyte permeability of lipid bilayer membranes, J. Gen. Physiol. 68:127.
GRANTHAM, J. J. and M. B. BURG. 1966. Effect of vasopressin and cyclic AMP on
permeability of isolated collecting tubules. Am. J. Physiol. 211:255-259.
GRAZIANi, Y., and A. LIVNE. 1971. Vasopressin and water permeability of artificial lipid
membranes. Biochem. Biophys. Res. Commun. 45:321-326.
HANDLER, J. S., and J. ORLO~F. 1973. T h e mechanism of action of antidiuretic hormone.
In Handbook of Physiology - Renal Physiology. S. R. Geiger, J. Orloff, and R. W.
Berliner, editors. T h e Williams and Wilkins Co., Baltimore. 791-814.
HAYS, R. M. 1972. The movement of water across vasopressin-sensitive epithelia. In
Current Topics in Membranes and Transport. F. Bonner and A. Kleinzeller, editors.
Academic Press, New York. 3:339-366.
Published August 1, 1976
A. FXNKELSTEIN Water PermeabilityIncrease Induced by ADH in Toad Bladder
143
HAYS, R. M., and A. LEAF. 1962. Studies on the movement of water t h r o u g h the isolated
toad b l a d d e r and its modification by vasopressin.J. Gen. Physiol. 45:905-919.
HLAVKY, S. B., and D. A. H^YI)ON. 1972. Ion transfer across lipid m e m b r a n e s in the
presence o f gramicidin A. I. Studies o f the unit conductance channel. Biochim. Biophys.
Acta. 274:294-312.
HoLz, R., and A. FINKELSTEIN. 1970• T h e water and nonelectrolyte permeability induced
in thin lipid m e m b r a n e s by the polyene antibiotics nystatin and amphotericin B.J. Gen.
Physiol. 56:125-145.
KOEFOED-JoHNSEN, V., and H. H. USSXNG. 1953. T h e contributions of diffusion and flow
to the passage o f D20 t h r o u g h living membranes. Effect of neurohypophyseal hormone on isolated a n u r a n skin. Acta Physiol. Scand. 28:60-76.
L~AF, A., and R. M. HAYS. 1962. Permeability o f the isolated toad b l a d d e r to solutes and
its modlfiCaUon by vasopressin.J. Gen. Physiol. 45:921-932.
LEVINE, S., N. FRANKI, and R. M. HAYS. 1973. Effect o f phloretin on water and solute
movement in the toad b l a d d e r . J . Clin. Invest. 52:1435-1442.
LEVINE, S~ D., R. D. LEVINE, R. E. WORTHINGTON,and R. M. HAYS. 1976. Selective
inhibition o f osmotic water flow by general anesthetics in toad urinary b l a d d e r . J . Clin.
Invest. In press.
MANNING, G. S. 1975. T h e relation between osmotic flow and tracer solvent diffusion for
single-file transport. Biophys. Chem. 5:147-152.
PIETRAS, R. J., and E. M. WRIGHT. 1974. Non-electrolyte probes of m e m b r a n e structure
in A D H - t r e a t e d toad urinary bladder. Nature (Lond.). 247:222-224.
PIETRAS, R. J., and E. M. WRXGHT. 1975. T h e m e m b r a n e action of antidiuretic h o r m o n e
(ADH) on toad urinary bladder. J. Membr. Biol. 22:107-123.
RUHLAND, W., and C. HOFFMANN. 1925. Die Permeabilit~it yon Beggiatoa mirabilis. Ein
Beitrag zur Ultrafiltertheorie des Plasmas. Planta. 1:1-83.
SCHAFER, J. A., S. L. TROUTMAN, and T. E. ANDREOLI. 1974. Osmosis in cortical
collecting tubules. A D H - i n d e p e n d e n t osmotic flow rectification. J. Gen. Physiol. 64:228240.
WRIGHT, E. M., and R. J. PIrTRAS. 1974. Routes o f nonelectrolyte permeation across
epithelial m e m b r a n e s . J . Membr. Biol. 17:293-312.
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