Conversion of Triglycylvasopressin to Lysine-Vasopressin in Man

Forsling, Mary L.; Aziz, L A; Ma, Miller; Davies, R.; Donovan, B.

doi:10.1677/joe.0.0850237

Cited by 71 publications

(36 citation statements)

References 9 publications

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“…In the first human study with terlipressin in five healthy subjects and in two early rat studies a decrease in diuresis was observed after terlipressin; however, these findings were never explored further (3,10,17). This lack of interest in antidiuresis was probably because people focused on the effects on bleeding.…”

Section: Discussionmentioning

confidence: 99%

Effects of terlipressin on the aquaretic system: evidence of antidiuretic effects

Krag¹,

Bendtsen²,

Pedersen³

et al. 2008

American Journal of Physiology-Renal Physiology

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Krag A, Bendtsen F, Pedersen EB, Holstein-Rathlou N-H, Møller S. Effects of terlipressin on the aquaretic system: evidence of antidiuretic effects. Am J Physiol Renal Physiol 295: F1295-F1300, 2008. First published August 27, 2008 doi:10.1152/ajprenal.90407.2008.-The vasopressin analog terlipressin is believed to cause vasoconstriction selectively by V 1 receptor stimulation. However, a possible antidiuretic effect by V 2 receptor stimulation has never been ruled out. Twenty-two patients with ascites, including seven with refractory ascites, were included. The subjects were studied during a 400 ml/h oral water load before and after infusion of 2 mg of terlipressin (18 patients) or placebo infusion (4 patients). Effects on the V 2 receptors were assessed by evaluating aquaporin (AQP)2 excretion, free water clearance (C H 2 O ), urine osmolality (Uosm), and fractional distal water excretion (DFeH 2O). After terlipressin the excretion of AQP2 increased by 89% [144 ng/mmol creatinine, 95% confidence interval (CI) 73-214 ng/mmol creatinine, P ϭ 0.001]. C H 2 O decreased 1.05 ml/min (from 0.17 to Ϫ0.89 ml/min, P ϭ 0.001), and DFeH 2O decreased 37% (19 vs. 12; 95% CI 2-11, P ϭ 0.01). U osm increased by 27% (93 mosmol/kgH 2O, 95% CI 23-164 mosmol/kgH2O, P ϭ 0.02). Plasma sodium decreased 1.1 mmol/l (P Ͻ 0.01). An increase in AQP2 excretion and a decrease in C H 2 O and distal water excretion after terlipressin despite water loading is a clear indication of activation of the antidiuretic system (V 2 receptor effect).aquaporin-2; vasopressin; hepatorenal syndrome; cirrhosis; ascites THE VASOPRESSIN ANALOG TERLIPRESSIN is widely used in the treatment of type 1 hepatorenal syndrome (HRS) (15,22). Patients with HRS are characterized by avid sodium and water retention. Terlipressin is believed to selectively cause vasoconstriction by stimulation of V 1 receptors (9). The V 1 receptors are predominantly located in the smooth muscles of the arterial vasculature in the splanchnic region (6). Terlipressin (triglycyllysine vasopressin) is an analog of the natural arginine vasopressin (AVP), which has affinity for both V 1 and V 2 receptors (24). AVP-induced V 2 receptor stimulation mediates water transport in the renal collecting ducts by increasing the number of aquaporin-2 water channels (AQP2) in the apical plasma membrane (2). V 2 receptors are located on the principal cells in collecting ducts in the kidney (24). V 2 receptor stimulation activates adenylyl cyclase, which increases intracellular cAMP concentration (2). Increased intracellular cAMP stimulates phosphorylation of the AQP2 protein, which is then translocated from intracellular vesicles to the apical membrane (2, 16). AVP regulates AQP2 in both an acute and a chronic manner. Short-term regulation by AVP involves trafficking of vesicles with AQP2 molecules to the apical membrane. cAMPstimulated transcription of the AQP2 gene is the long-term regulation of AQP2 (2, 16). Release of AVP from posterior pituitary gland is controlled by osmoreceptors in the anterior hypo...

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Section: Discussionmentioning

confidence: 99%

Effects of terlipressin on the aquaretic system: evidence of antidiuretic effects

Krag¹,

Bendtsen²,

Pedersen³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…Lysine-vasopressin was determined (as described by Forsling, Aziz, Miller, Davies & Donovan, 1980) by radioimmunoassay using plasma extracted with Fuller's earth (Skowsky, Rosenbloom & Fisher, 1974). Synthetic lysine-vasopressin (Ferring, Malmo) was used as standard and for preparation of labelled peptide by the lactoperoxidase method.…”

Section: Blood Collectionmentioning

confidence: 99%

The milk ejection reflex in the pig

Ellendorff

Forsling

Poulain³

1982

The Journal of Physiology

104

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SUMMARY1. The milk ejection reflex in response to suckling was studied in conscious sows by continuous recording of intramammary pressure, radioimmunoassay of plasma concentrations of neurohypophysial hormones, and observation of the behaviour of the sows and piglets.2. A regular pattern of nursing, suckling and milk ejection was observed. The mean duration of the suckling period was 6-3 min. Over 144 suckling periods, 113 milk ejections were recorded. Each milk ejection was characterized by a sudden rise in intramammary pressure reaching 20-49 mmHg, and lasting 8-41 sec. Milk ejections occurred only once per suckling period, at a mean interval of 44-3 min.3. Each milk ejection occurred with a mean latency of 2-4 min from the onset of a period of initial massage of the udders by the piglets, and was coincident with a period of quiet suckling when the piglets were consuming milk. The onset of nursing was signalled by the sows grunting in a rhythmic manner. In most cases, the frequency of grunts, at first low, increased suddenly 23 see before milk ejection. 4. During eighteen suckling periods leading to milk ejection, neurohypophysial hormone assays performed on serial blood samples showed an increase in plasma concentration of oxytocin up to 30 see before milk ejection. The concentration of lysine-vasopressin did not rise above basal levels.5. In 21-4% of the suckling periods, no rise in intramammary pressure was observed. In these 'incomplete sucklings', the sow usually failed to grunt rapidly, and the piglets obtained no milk. For three of these periods, hormone assay showed no increase in oxytocin or vasopressin concentrations in blood.6. Oxytocin given intravenously produced variations in intramammary pressure which depended on the dose and the rate of injection. Rapid injections of 25-50 m-u. oxytocin, caused milk ejections similar to those induced by suckling. When oxytocin was administered at different rates, the faster the injection, the shorter the latency and the higher the amplitude of the response. Plasma concentrations of oxytocin after injection of 25 m-u. were similar to those observed during reflex milk ejection.7. Trains of electrical pulses were applied to the posterior pituitary of four anaesthetized sows. At frequencies ofstimulation above 10 Hz, a rise in intramammary The experiments were carried out at the Instutit fur Tierzucht und Tierverhalten, Mariensee. 19 PHY 333 F. ELLENDORFF, M. L. FORSLING AND D. A. POULAIN pressure and an increase in plasma oxytocin and vasopressin concentrations were observed. At frequencies of stimulation of 30-50 Hz, the response of the mammary gland and the time course of the variations in oxytocin plasma concentrations were similar to those observed during natural reflex milk ejection.8. It is concluded that reflex milk ejections during suckling in the pig are caused by the intermittent and spurt-like release of about 25 m-u. oxytocin, without concomitant vasopressin release. It is postulated that the release of oxytocin is probably precipitated by a brie...

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“…Once formed, lysine-vasopressin is eliminated by plasma peptidase losing its vasopressinergic activity. 36,37 There is a biphasic decline in plasma terlipressin concentration, with an elimination half-life of 50 minutes. Terlipressin administration results in a marked increase in plasma concentrations of lysine-vasopressin, which peaks at 60-120 minutes, and remains elevated for at least 180-240 minutes.…”

Section: Discussionmentioning

confidence: 99%