Biomedical subjects
Publications and source records attributed to A W Cuthbert.
Treatment of the serosal surface of the isolated bladders of toads (Bufo marinus) with phospholipase C inhibited the hydro-osmotic response to ADH, but did not prevent the rise in cyclic AMP concentrations associated with hormone action.
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1. The sodium-dependent oxygen consumption of pieces of toad bladder (Bufo marinus) has been investigated using an oxygen electrode.2. The effect of polyvalent cations (Ca(2+), Sr(2+), Mg(2+), Eu(3+), La(3+) and Mn(2+)) on sodium-dependent oxygen consumption has been measured. All cations inhibited oxygen consumption, the order of effectiveness being Ca(2+) > Sr(2+) > Mg(2+) > Mn(2+) > Eu(3+) > La(3+).3. Treatment of bladder pieces with antidiuretic hormone (50 m-u./ml.) decreased the effectiveness of Ca(2+) and Sr(2+) as inhibitors of sodium-dependent oxygen consumption. Mn(2+), Eu(2+) and La(2+) were more effective after hormonal treatment, while the effectiveness of Mg(2+) was unaltered.4. The results have been interpreted in terms of a model in which sodium entry to the transporting mechanisms of the epithelium is controlled by Ca(2+), and in which antidiuretic hormone alters Ca(2+) binding and so affects sodium transport.
1. Preparations bathed in a well stirred solution have been considered as heterogeneous systems in which the solid phase is enveloped by a thin layer of stationary liquid. Any substance applied into the bulk solution must pass through this layer by diffusion before reaching the receptors.2. The rate of diffusion through the stationary layer can govern the time course of the cellular responses to applied drugs provided that (i) all receptors involved in the response are situated at an equal distance from the solution and (ii) interaction with the receptor and consequent cellular events are very rapid.3. These conditions have been verified for two responses: the contraction of guinea-pig ileum by acetylcholine (ACh), carbamylcholine (CCh), histamine and KCl, and the depolarization of the rat isolated sympathetic ganglion by ACh in the presence of eserine. A method of analysis has been applied which allows a complete dose-response curve to be obtained from only two responses.4. Diffusion half-times measured for pieces of ileum were 4.13 +/- 0.13 s (S.E. of mean) for Ach, 3.60 +/- 0.05 s for CCh and 1.01 + 0.05 s for KCl. The equivalent thickness of the stationary layer calculated from these values was respectively 93 mum, 87 mum and 70 mum. The average diffusion half-time for ACh in sympathetic ganglia was 14.19 +/- 1.05 s. This gives an equivalent thickness of 173 mum.5. Diffusion half-times were increased by increasing the viscosity of the bathing solution without changing the concentration response relationship.6. The time course of contractions of guinea-pig ileum are no longer diffusion limited in the presence of a competitive antagonist or when the temperature is lowered from 35 degrees to 25 degrees C.
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1. The instantaneous impedance method has been used to study the effects of antidiuretic hormone (ADH) on frog skin.2. The resting skin may be represented by a parallel RC network with a single time constant.3. Antidiuretic hormone causes an increase in conductance and capacitance and in some cases the appearance of a polarization angle.4. The structures in the skin responsible for the transients are located in the outermost membranes.5. The effects of ADH have been interpreted in terms of the formation of water-filled sodium-permselective pores in the outer facing membranes which occupy, at most, 0.3% of the skin surface. These pores constitute a parallel, and hence additive, capacitance with that of the normally ion impermeable parts of the cell surface, and in addition are responsible for the increase in conductance. The polarization angle is due to the polydisperse nature of the skin after hormone treatment.
1. Substitution of chloride by isethionate reduces the short circuit current (SCC) and increases the potential of isolated frog skin. In sodium isethionate Ringer antidiuretic hormone and choline chloride increase the SCC, whereas theophylline is ineffective.2. Frog skins treated on the outside with copper ions always show an increased potential when bathed in normal Ringer solution. The SCC may be moderately increased or decreased.3. Theophylline increases skin thickness and cell volume in non-short-circuited skins.4. The ways in which the theophylline-induced increase in chloride permeability affects sodium transport is discussed, together with the requirements for a permeant anion in both short- and open-circuited skins.
1. Impedance loci for frog skins have been calculated by computer analysis from voltage transients developed across the tissues.2. Attention has been paid to simultaneous changes in conductance and capacitance of skins treated either with antidiuretic hormone (ADH) or with theophylline. These drugs always caused an increase in conductance and usually the skin capacitance also increased. However, changes in conductance were not correlated with capacitance changes.3. Changes in capacitance caused by the drugs may represent pore formation in the barrier to water flow, since both drugs increase hydro-osmotic flow in epithelia. If this interpretation is correct, then 0.14% of the membrane area forms water-permeable pores in response to a maximal dose of ADH. This value is somewhat less than the value obtained previously (0.3%) by graphical analysis.4. A theoretical account is given of the relative accuracy of the computer method and the graphical method for voltage transient analysis.
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1. The effects of antidiuretic hormone (ADH), theophylline and cyclic 3',5'-adenosine monophosphate (AMP) on membrane potentials in frog skin have been investigated.2. Membrane potentials across the outer and inner facing membranes were recorded in both normal and current clamped skins. In the latter condition active transport of sodium had been abolished by ouabain or metabolic inhibitors, but ionic gradients were maintained by passing current through the skin from the inside.3. ADH increases the potential across the outer facing membranes and reduces the skin resistance. The results are consistent with ADH causing an increase in permeability of the outer facing membranes to sodium ions.4. Theophylline reduces the skin potential by reducing specifically the potential across the outer facing membranes. At the same time the skin resistance is reduced. Theophylline acts by increasing the permeability of the outer facing membranes to chloride ions.5. Cyclic 3',5'-AMP causes a biphasic potential change accompanied by an increase in skin resistance.6. Metabolic inhibitors block the response of the skin to ADH but not to theophylline.7. Separate explanations for the increase in sodium transport by ADH, theophylline and cyclic 3',5'-AMP are discussed. It is not necessary to involve cyclic AMP in order to explain the effects of either ADH or theophylline.
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