Selective Agonists and Antagonists of Vasopressin

Manning, Maurice; Bańkowski, Krzysztof; Sawyer, Wilbur H.

doi:10.1007/978-1-4615-8129-1_8

Cited by 92 publications

(117 citation statements)

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“…Highly potent and selective V, agonists V, agonists that are more potent and selective than the hormone arginine-vasopressin have been discovered (Manning et al 1987). Deamino-8-D-arginine-vasopressin (dDAVP;Zaoral et al 1967) is 4 four times more potent that vasopressin (1200 U mg-' vs. 323 U mg-'; Manning et al 1987).…”

Section: Resultsmentioning

confidence: 99%

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Discovery and design of novel and selective vasopressin and oxytocin agonists and antagonists: the role of bioassays

Çhan¹,

Wo²,

Stoev³

et al. 2000

Experimental Physiology

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Synthetic oxytocin and vasopressin agonists and antagonists have become important tools for research and were instrumental in the identification of the four known receptor subtypes, Via, V,, V,, (V,) and oxytocin, of these peptide hormones. However, the relative lack of receptor selectivity, particularly of the antagonists, has limited their usefulness as experimental probes and their potential as therapeutic agents. We now present some findings from our continuing studies aimed at the design of more selective oxytocin and vasopressin agonists and antagonists and a structure-activity relationship update on our recently discovered novel hypotensive vasopressin peptides. Bioassays have been, and continue to be, of critical importance in leading to the discovery of the novel agonists, antagonists and hypotensive peptides reported here. This paper highlights three main aspects of these studies. (1) Replacement of the tyrosine' and/or phenylalanine3 residues in the V, agonist deamino,[Va14, ~-Arg~]arginine-vasopressin (dVDAVP) by thienylalanine resulted in selective V, agonists with strikingly high potencies. However, the peptide solutions were unstable and lost activity over time. These highly potent V, agonists, which are devoid of vasopressor activity, are promising leads for improving drugs for treating diabetes insipidus, enuresis and coagulation disorders. (2) (1895) injected an extract of the pituitary gland into an anaesthetised dog and found that the extract had a potent vasopressor activity. A decade later, Dale (1906) while studying the vasopressor action of the pituitary extract discovered that the extract also possessed a powerful stimulating action on Ihe smooth muscle of the uterus. These observations were the first experimental evidence that ultimately established the biological functions of the posterior pituitary gland and its hormones: vasopressin and oxytocin. The two historical findings were incidental discoveries uncovered during an exploration of the biological activities of pituitary extracts in intact whole animal experiments. The overriding theme of this review is the discovery of a series of novel, selective, hypotensive vasopressin peptides. Like the pioneering work noted above, the hypotensive activity of these vasopressin peptides was also discovered incidentally while we were carrying out bioassay characterisations on a series of newly designed vasopressin V, receptor antagonists aimed at developing more selective and potent V, receptor antagonists.Publication of The Physiological Society

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Section: Resultsmentioning

confidence: 99%

“…Deamino-8-D-arginine-vasopressin (dDAVP;Zaoral et al 1967) is 4 four times more potent that vasopressin (1200 U mg-' vs. 323 U mg-'; Manning et al 1987).…”

Section: Resultsmentioning

confidence: 99%

Discovery and design of novel and selective vasopressin and oxytocin agonists and antagonists: the role of bioassays

Çhan¹,

Wo²,

Stoev³

et al. 2000

Experimental Physiology

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“…Stimulation of vasopressinergic neurons by neuro transmitters and neuromodulators induces a release of AVP, eventually causing antidiuresis through the renal AVP (V2) receptors (11,12). By injecting various drugs into the SON or PVN, we have previously shown that cholinergic (13,14), adrenergic (15,16) and enkephaliner gic mechanisms (17,18) may control the urine outflow through a stimulation of AVP release.…”

mentioning

confidence: 99%

Blockade of Retinal NMDA Receptors by Sodium Nitroprusside Is Probably Due to Nitric Oxide Formation

Ujihara

Akaike

Tsutsumi

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-The effects of injection of substance P (SP) into the hypothalamic supraoptic vasopres sinergic nucleus (SON) in water-loaded and ethanol-anesthetized rats were examined. Keywords:Substance P, Antidiuresis, Supraoptic nucleus, Vasopressin, Substance P antagonist Substance P (SP), a member of the tachykinin family of bioactive peptides, is suggested to be a neurotransmit ter or a neuromodulator in the central and peripheral nervous system (1 3). Immunohistochemical studies have shown that SP terminals are found not only in the spinal cord (4) and the substantia nigra (5), but also in the hypothalamus (6, 7). Therefore, the involvement of SP in physiological functions in the hypothalamus such as stimulation of arginine-vasopressin (AVP), growth hor mone and prolactin release has been suggested (8 10).The hypothalamic supraoptic nucleus (SON), as well as the paraventricular nucleus (PVN), contains cell bodies of vasopressinergic neurons that synthesize and release AVP. Stimulation of vasopressinergic neurons by neuro transmitters and neuromodulators induces a release of AVP, eventually causing antidiuresis through the renal AVP (V2) receptors (11,12). By injecting various drugs into the SON or PVN, we have previously shown that cholinergic (13,14), adrenergic (15, 16) and enkephaliner gic mechanisms (17, 18) may control the urine outflow through a stimulation of AVP release.The vasopressinergic cell bodies in the SON or PVN make synaptic contact with SP-containing nerve termi nals (6). It was demonstrated that intraventricular injec tion of SP induced a prolonged antidiuresis in water-load ed rat (19) and an increase in firing frequency of the SON (20). However, the effect of SP microinjected directly into the vasopressinergic nuclei on the AVP release remains un clear. In this study, we examined the effects of SP and its analog [D-Pro2, D-Trp'°9]SP on the outflow, osmotic pres sure and AVP level of urine by injection into the SON in water-loaded and ethanol-anesthetized rats. The influ ences of pretreatments with AVP-receptor, SP-receptor and muscarinic receptor antagonists on the SP-induced antidiuresis were also examined. The present data showed that SP causes antidiuresis through the release of AVP. MATERIALS AND METHODS Animals and drugsMale Wistar rats, weighing 280-330 g, were used.

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“…In recent years. potent V, and V2 antagonists of vasopressin have been developed (for review see Manning et al, 1987) which were used to investigate the physiology and pathophysiology of vasopressin. A large number of these compounds contain in position 1 of the vasopressin sequence either (deamino)penicillamine or 3-mercapto-3,3-cyclopentaniethylene propionic acid (Mca) instead of cysteine.…”

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confidence: 99%

Conformation of [8‐arginine]vasopressin and V₁ antagonists in dimethyl sulfoxide solution derived from two‐dimensional NMR spectroscopy and molecular dynamics simulation

Schmidt

Ohlenschläger

Rüterjans

et al. 1991

European Journal of Biochemistry

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Structural and dynamic properties of [8-arginine]vasopressin and a class of highly potent vasopressin V I antagonists which contain 3-mercapto-3,3-cyclopentamethylene propionic acid (Mca) in position 1 of the vasopressin sequence have been determined. On the basis of two-dimensional N M R experiments in dimethyl sulfoxide solution, interproton distances were derived according to which model conformations were built and refined using molecular dynamics simulations. The conformation of vasopressin and the V1 antagonists differ mainly in the region of the mutated residue. The antagonistic property was found to be related to an inversed chirality of the disulfide bridge. In all investigated molecules, characteristic fl-turn structure elements were found f o r the backbone conformation of the endocyclic residues Tyr2-Asn5. For this portion of the peptide sequence, various conformational equilibria were detected which matched different time scales. For [Arg8]vasopressin, averaged N M R parameters were obtained which could be explained by rapid interconversion between different B-turn geometries, whereas multiple slowly exchanging conformations were observed for the V1 antagonists. V antagonists containing sarcosine in position 7 exhibited multiple spectral patterns for the exocyclic part attributed to ci.s/trnns isomerization. The X-ray structure of deamino-oxytocin [Wood, S. P., Tickle, I.

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Selective Agonists and Antagonists of Vasopressin

Cited by 92 publications

References 131 publications

Discovery and design of novel and selective vasopressin and oxytocin agonists and antagonists: the role of bioassays

Discovery and design of novel and selective vasopressin and oxytocin agonists and antagonists: the role of bioassays

Blockade of Retinal NMDA Receptors by Sodium Nitroprusside Is Probably Due to Nitric Oxide Formation

Conformation of [8‐arginine]vasopressin and V₁ antagonists in dimethyl sulfoxide solution derived from two‐dimensional NMR spectroscopy and molecular dynamics simulation

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Selective Agonists and Antagonists of Vasopressin

Cited by 92 publications

References 131 publications

Discovery and design of novel and selective vasopressin and oxytocin agonists and antagonists: the role of bioassays

Discovery and design of novel and selective vasopressin and oxytocin agonists and antagonists: the role of bioassays

Blockade of Retinal NMDA Receptors by Sodium Nitroprusside Is Probably Due to Nitric Oxide Formation

Conformation of [8‐arginine]vasopressin and V1 antagonists in dimethyl sulfoxide solution derived from two‐dimensional NMR spectroscopy and molecular dynamics simulation

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Conformation of [8‐arginine]vasopressin and V₁ antagonists in dimethyl sulfoxide solution derived from two‐dimensional NMR spectroscopy and molecular dynamics simulation