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Search for other papers by M. GINSBURG in
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SUMMARY
1. The antidiuretic potency of arterial blood from adrenalectomized rats was greater than that from intact rats, but only if 2 or more ml. of blood were taken from each rat. It is concluded that the amounts of posterior pituitary antidiuretic hormone released during haemorrhage are greater in adrenalectomized than in intact rats.
2. The effect of haemorrhage on the antidiuretic potency of blood in adrenalectomized rats treated with sodium chloride or cortisone was not different from that in intact rats.
3. The disappearance of intravenously injected vasopressin (100 mU/100 g body weight) was retarded after adrenalectomy. Up to 48 hr after adrenalectomy this was due to a reduced capacity of the kidneys to remove vasopressin from the circulation.
4. Treatment with cortisone increased the rate of disappearance of vasopressin in adrenalectomized rats, but the rate was not restored to that observed in intact animals.
5. Treatment with sodium chloride did not affect the rate at which vasopressin was removed from the circulation of adrenalectomized rats.
6. The excretion of an antidiuretic agent in the urine which followed intravenous injection of vasopressin (100 mU/100 g) 48 hr after adrenalectomy was equivalent to 2·1% of the dose. This compared with an excretion of 6·7% of the dose in intact animals.
Search for other papers by A. D. STEWART in
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SUMMARY
Adenyl cyclase was measured in vitro in renal medullary homogenates from male mice of the Peru and CBA/FaCam strains. The basal activity of adenyl cyclase was increased on incubation with 30 mm-NaF and with varying concentrations of [8-arginine]-vasopressin (AVP) and [8-lysine]-vasopressin (LVP) up to 100 mu./ml. In both strains of mice, the maximal hormone activation was the same whichever vasopressin was used, and the same degree of stimulation was observed on incubation of homogenates with both hormones together. It is concluded that both hormones have the same intrinsic activity in this system, and are acting on the same population of receptors within each strain of mouse.
Half-maximal adenyl cyclase activation was achieved with 240 ± 50 (s.e.m.) μu. AVP/ml and 920 ± 160 μu. LVP/ml in homogenates from CBA/FaCam mice; and 240 ± 40 μu. AVP/ml and 1900 ± 250 μu. LVP/ml in Peru mice. These results are compared with previously reported potencies in these mice of the two vasopressins as antidiuretic agents in vivo. Whilst there is good agreement between results in vitro and in vivo with CBA/FaCam mice, there is a highly significant discrepancy with Peru mice. Explanations for these results, including the possibility that cyclic AMP may not be the sole mediator of the increased water permeability of the distal tubule induced by vasopressin, are discussed.
Search for other papers by P. J. BENTLEY in
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SUMMARY
1. The effects of metabolic inhibitors and ionic changes on the short-circuit current across the toad's bladder have been studied both in the presence and absence of vasopressin.
2. The effects of metabolic inhibitors indicate that the energy for short-circuit current is derived from both glycolysis and oxidative metabolism.
3. Divalent ions play an important part in the maintenance of the resting short-circuit current and of its response to vasopressin. Ca++ or Sr++ are necessary for the former and Ca++ for the latter.
4. Increased concentration of Ca++, Sr++, Mg++ or Ba++ did not inhibit the increment in short-circuit current produced by vasopressin, in contrast to the effect of these ions on water transport.
5. Increase and decrease in potassium concentration inhibited the short-circuit current whether vasopressin was present or not.
6. The correct concentration of sodium on the serosal side of the bladder was necessary to maintain the short-circuit current, but the increment seen when vasopressin was added was not affected by 50% substitution of choline for sodium.
Search for other papers by H. Vilhardt in
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Search for other papers by S. Lundin in
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ABSTRACT
Using implanted minipumps it was shown over a period of 7 days that the vasopressin antagonist, 1-deamino-pentamethylene-2-d-Phe-4-Ile-arginine vasopressin, caused increased diuresis in normal rats and reversed vasopressin- or oxytocin-induced antidiuresis in Brattleboro rats. When the antagonist was infused alone in Brattleboro rats it induced a marked antidiuretic response, indicating that the analogue also possessed agonistic properties. The agonist action could not be demonstrated in anaesthetized, hydrated normal rats. In these animals the analogue behaved as a pure antagonist. It is concluded that analogues which behave as antagonists in one test model may display agonistic properties under different experimental conditions.
J. Endocr. (1987) 112, 439–442
Search for other papers by JANE G. BUCHANAN in
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Search for other papers by A. D. STEWART in
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Desert-living kangaroo rats (Dipodomys merriami) have large neurohypophysial stores of vasopressin compared with rodents from non-arid environments (Ames & van Dyke, 1950). This presumably contributes to the animals' ability to produce very concentrated urine for extended periods (Schmidt-Nielsen, 1964). We have investigated the pituitary store of vasopressin in another rodent adapted to arid environments, the Mongolian gerbil (Meriones unguiculatus), both when allowed free access to water, and after 7 days of water deprivation. Young adult gerbils (ten males and ten females) were obtained from a commercial supplier and kept in our laboratory with free access to food and water for 2 weeks before experimentation began.
The animals were divided into two equal groups both kept at 30 °C and 30 ± 4% relative humidity. One group (control) was allowed free access to food (Edinburgh University rat cake) and water; the other group (dehydrated) was allowed food only. Vasopressin was assayed
Search for other papers by L. M. Burrell in
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ABSTRACT
A non-peptide, orally effective, vasopressin (AVP) V1 receptor antagonist 1-{1-[4-(3-acetylaminopropoxy) benzoyl]-4-piperidyl}-3,4-dihydro-2(1H)-quinolinone (OPC-21268) has recently been described. This paper reports the in-vitro and in-vivo characterization of OPC-21268 binding to vasopressin receptors in rat liver and kidney.
OPC-21268 caused a concentration-dependent displacement of the selective V1 receptor antagonist radioligand, 125I-labelled [d(CH2)5,sarcosine7]AVP to V1 receptors in both rat liver and kidney medulla membranes. The concentration of OPC-21268 that displaced 50% of specific AVP binding (IC50) was 40±3 nmol/l for liver V1 and 15±2 nmol/l for kidney V1 receptors (mean ± s.e.m.; n = 3). OPC-21268 had little effect on the selective V2 antagonist radioligand [3H]desGly-NH2 9[d(CH2)5,d-Ile2,Ile4] AVP binding to V2 receptors in renal medulla membranes (IC50 >0·1 mmol/l).
After oral administration to rats, OPC-21268 was an effective V1 antagonist in a time- and dose-dependent manner. Binding kinetic studies showed that OPC-21268 acted as a competitive antagonist at the liver V1 receptor in vitro and in vivo, in addition to its in-vitro competitive effects at the renal V1 receptor. OPC-21268 shows promise as an orally active V1 antagonist.
Journal of Endocrinology (1993) 138, 259–266
Search for other papers by P. J. BENTLEY in
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SUMMARY
N-Ethylmaleimide (NEM) prevents the hydro-osmotic response to vasopressin. It has no significant effects on osmotic water movement in the absence of the hormone. The hydro-osmotic effects of cyclic AMP and hyperosmotic mannitol solutions are also reduced by NEM.
After exposure to vasopressin, cyclic AMP, or hyperosmotic mannitol, the osmotic permeability declines to the preincubation level but after exposure to NEM this was prevented. This effect was seen after exposure to 10−4 and 10−5 m-NEM, i.e. concentrations that do not alter the onset of the response.
The increased osmotic permeability after treatment with NEM is not due to a non-specific effect caused by a 'fixation' of the tissue in a distorted condition (such as occurs during rapid water transfer) since it was seen even after treatment of the tissue under conditions when no osmotic water movement was occurring, that is with iso-osmotic Ringer solution on both sides.
The effect of NEM could not be mimicked by exposure of the bladder to 20 mm-Ca2+, 0·1 mm-Zn2+ or 1 mm-l-cysteine.
Search for other papers by P. J. BENTLEY in
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SUMMARY
The electrical potential difference and short-circuit current (scc, reflecting active transmural sodium transport) across the toad urinary bladder in vitro was unaffected by the presence of hypo-osmotic solutions bathing the mucosal (urinary) surface, providing that the transmural flow of water was small.
Vasopressin increased the scc across the toad bladder (the natriferic response), but this stimulation was considerably reduced in the presence of a hypo-osmotic solution on the mucosal side, conditions under which water transfer across the membrane was also increased.
This inhibition of the natriferic response did not depend on the direction of the water movement, for if the osmotic gradient was the opposite way to that which normally occurs, the response to vasopressin was still reduced.
The natriferic response to cyclic AMP was also inhibited in the presence of an osmotic gradient. Aldosterone increased the scc and Na+ transport across the toad bladder but this response was not changed when an osmotic gradient was present.
The physiological implications of these observations and the possible mechanisms involved are discussed.
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Search for other papers by L. SALAMONSON in
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SUMMARY
A radioimmunoassay method for the measurement of arginine-vasopressin (AVP) in human plasma has been developed which requires 5 ml of plasma and has a lower limit of detection of 1·8 pg/ml plasma. Arginine-vasopressin was found to be stable in whole blood for up to 1 h at room temperature and for at least 4 h at 4 °C, while in plasma stored at − 20 °C no loss was seen over 10 days. Dehydration and rehydration in normal subjects produced appropriate changes in AVP concentration but there was considerable variability in the levels attained by individual subjects and no obvious correlation with plasma osmolality. No consistent increase in plasma AVP concentration was seen on change of posture from the recumbent to the upright position. Vigorous exercise produced a marked rise in plasma AVP concentrations in most subjects which could not be attributed simply to an increase in plasma osmolality. Infusion studies with Pitressin in normal subjects showed a mean halflife of 6·4 min with an overall plasma clearance rate of 8·5 ml/min/kg body weight and a mean volume of distribution of 5·33 1. In patients with a biochemical picture suggestive of inappropriate antidiuretic hormone secretion, markedly raised plasma AVP concentrations were found only in patients with bronchial carcinoma.
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ABSTRACT
The present study was performed to examine the effect of the cyclo-oxygenase inhibitor, indomethacin, and that of various prostaglandins on the release of vasopressin and β-endorphin-like immunoreactivity (β-EI) from the rat neurointermediate lobe of the hypophysis, which was superfused in vitro. Indomethacin (2·8 and 28 μmol/l) changed neither basal secretion of vasopressin nor that evoked by electrical stimulation, whereas the resting release of β-EI was enhanced by indomethacin (28 μmol/l). Prostaglandin (PG) E2 did not influence resting release of vasopressin but markedly inhibited (by about 50%) electrically induced release of vasopressin (least effective concentration: 300 nmol/l) as well as spontaneous secretion of β-EI (least effective concentration: 100 nmol/l) in the presence of indomethacin (28 μmol/l). Prostaglandin F2α (5 μmol/l) also inhibited the evoked release of vasopressin, whereas PGD2 (5 μmol/l) did not. Prostaglandin F2α (5 μmol/l), D2 and I2 (1·5 μmol/l each) produced no effects on β-EI release. As observed in the neurohypophysis, PGE2 inhibited the electrically induced release of vasopressin from the medial basal hypothalamus in vitro. We conclude that prostaglandins (especially PGE2) can inhibit (1) the stimulated release of vasopressin when acting on vasopressin-containing nerve terminals of either neurosecretory system (neurohypophysis, median eminence region), and (2) the secretion of β-EI and, as can be inferred, α-MSH, by a direct action on intermediate lobe cells.
J. Endocr. (1985) 106, 189–195
