Critical Differences Between Species in the In Vivo and In Vitro Renal Responses to Antidiuretic Hormone Antagonists

Fl, Stassen; Bryan, William M.; Gross, Milton D.; Kavanagh, Brian P.; Shue, D.; Sulat, L; Vd, Wiebelhaus; N, Yim; Lb, Kinter

doi:10.1016/s0079-6123(08)64406-4

Cited by 19 publications

(2 citation statements)

References 9 publications

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“…During chronic administration of these AVP analogues their an¬ tagonist actions on the antidiuretic effect of AVP are lost, revealing instead AVP agonistic effects (Hofbauer et al 1986, Brooks et al 1988, Mah & Hofbauer 1988, Albrightson-Winslow et al 1989). There are also species differences in the antagonistic effect of AVP analogues on the antidiuretic action of AVP (Stassen et al 1983). This is a serious problem, because the same AVP analogues cannot antagonize in both monkeys and man.…”

Section: Introductionmentioning

confidence: 99%

In vivo diuretic effect of a new non-peptide arginine vasopressin antagonist, OPC-31260, in conscious rats

Tsuboi

Ishikawa²,

Fujisawa³

et al. 1994

Journal of Endocrinology

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The present study was undertaken to determine whether a non-peptide arginine vasopressin (AVP) antagonist (5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetra hydro-1H- benzazepine; OPC-31260) antagonizes the antidiuretic action of endogenous and exogenous AVP in conscious rats. OPC-31260, given orally at a dose of 5 mg/kg or higher, increased urinary volume (UV) and reduced urinary osmolality (Uosm) in a dose-dependent manner, in rats acutely denied access to water. Minimal Uosm was obtained 1-2 h after oral administration of OPC-31260. OPC-31260 caused sustained water diuresis for more than 12 h when water was available ad libitum since OPC-31260 (30 mg/kg) reduced Uosm to less than 230 mOsmol/kg H2O, significantly less than the control value of 600 mOsmol/kg H2O. Water deprivation for 24 h increased plasma AVP levels to 7.2 pmol/l and increased Uosm to 2160 mOsmol/kg H2O. In such water-deprived rats, oral administration of OPC-31260 at 100 mg/kg was diuretic; it markedly increased free water clearance and decreased Uosm to 202 mOsmol/kg H2O. In homozygous Brattleboro rats (with inherited AVP deficiency), given free access to water, subcutaneous infusion of the V2 agonist 1-deamino-8-D-AVP (dDAVP) at a rate of 1 ng/h markedly decreased UV to 12.6 from 148.7 ml/day and increased Uosm to 1762 from 231 mOsmol/kg H2O. OPC-31260 (30 mg/kg) promptly increased UV and reduced Uosm to levels similar to those before the administration of dDAVP; repeated OPC-31260 treatment had sustained effects. These results indicate that OPC-31260 is an orally effective non-peptide AVP antagonist to the antidiuretic action of AVP in the conscious rat.

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Section: Introductionmentioning

confidence: 99%

In vivo diuretic effect of a new non-peptide arginine vasopressin antagonist, OPC-31260, in conscious rats

Tsuboi

Ishikawa²,

Fujisawa³

et al. 1994

Journal of Endocrinology

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“…The differences in the a [d(CH2)5-D-Ile2,jle4]AVP for the Via receptors of rat and hunp liver probably reflect a genuine species difference. Such species differences have been noticed by others when studying vasopressin antagonists in the rat and dog (Liard et al, 1982;Stassen et al, 1983). The 10-fold lower affinity of[d(CH2)5-Tyr(Me)2]AVP for the human Vla receptor compared with the rat receptor would explain why [3H]AVP proved to be a better tracer ligand than [3H][d(CH2)5-Tyr(Me)2]AVP for human tissue.…”

Section: Discussionmentioning

confidence: 62%

Characterization of the human liver vasopressin receptor. Profound differences between human and rat vasopressin-receptor-mediated responses suggest only a minor role for vasopressin in regulating human hepatic function

Howl

Ismail

Strain

et al. 1991

Biochemical Journal

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The [Arg8]vasopressin (AVP) receptor expressed by human hepatocytes was characterized, and compared with the rat hepatic V1a vasopressin receptor subtype. In addition to determining the pharmacological profile of the human receptor, the cellular responses to AVP were measured in human and rat hepatocytes by assaying glycogen phosphorylase alpha activity and DNA synthesis. Marked differences were observed between human and rat hepatocytes regarding vasopressin receptors and the intracellular consequences of stimulation by AVP. Data presented in this paper demonstrate the following, (i) Vasopressin V1a receptors are present in low abundance on human hepatocytes. (ii) Species differences exist between human and rat V1a receptors with respect to the affinity of some selective antagonists. (iii) AVP-stimulated glycogen phosphorylase a activation in human hepatocytes was approx. 5% of that observed in rat cells. (iv) In contrast with rat hepatocytes, DNA synthesis in human cells in culture was not stimulated by AVP. It is concluded that vasopressin plays only a minor role in the regulation of human hepatic function. Furthermore, conclusions drawn from observations made with AVP and its analogues on rat hepatic function cannot be directly extrapolated to the human situation.

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Discovery of Nonpeptide Vasopressin V2 Receptor Antagonists

Kondo

Ogawa

2012

Analogue‐Based Drug Discovery III

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Critical Differences Between Species in the In Vivo and In Vitro Renal Responses to Antidiuretic Hormone Antagonists

Cited by 19 publications

References 9 publications

In vivo diuretic effect of a new non-peptide arginine vasopressin antagonist, OPC-31260, in conscious rats

In vivo diuretic effect of a new non-peptide arginine vasopressin antagonist, OPC-31260, in conscious rats

Characterization of the human liver vasopressin receptor. Profound differences between human and rat vasopressin-receptor-mediated responses suggest only a minor role for vasopressin in regulating human hepatic function

Discovery of Nonpeptide Vasopressin V2 Receptor Antagonists

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