No requirement of cyclic conformation of antagonists in binding to vasopressin receptors

Manning, Maurice; Przybylski, Jacek; Olma, Aleksandra; Kliś, Wieslaw A.; Kruszynski, Marian; Wo, Nga Ching; Pelton, Gregory H.; Sawyer, Wilbur H.

doi:10.1038/329839a0

Cited by 78 publications

(35 citation statements)

References 13 publications

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“…Very recently, a new series of antagonists lacking the usual hexapeptide ring structure have been synthesized (Manning et al, 1987b(Manning et al, , 1990Schmidt et al, 1991). Some of these linear ligands were very high affinity vasopressin antagonists.…”

Section: Discussionmentioning

confidence: 99%

“…More recent developments in the design of VPR antagonists have shown that linear analogues of [Arg'IVP can also bind with high affinity to VPR (Manning et al, 1987b(Manning et al, , 1990Schmidt et al, 1991). One such peptide, (PhAcAVP; [l-phenylacetyl, 2-O-methyl-D-tyrosine, 6-arginine, 8-arginine, 9-tyrosinamide]vasopressin) is a very high-affinity and V1,-selective antagonist (Schmidt et al, 1991).…”

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confidence: 99%

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Fluorescent and biotinylated linear peptides as selective bifunctional ligands for the V_1a vasopressin receptor

Howl

Wang

Kirk

et al. 1993

European Journal of Biochemistry

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We have designed and synthesized a linear peptide analogue of arginine vasopressin. This peptide, 11-phenylacetyl, 2-O-methyl-~-tyrosine, 6-arginine, 8-arginine, 9-lysinamide]vasopressin (PhAcALVP), has a lysinamide residue substituted for the more usual glycinamide at position 9. Derivatization of PhAcALVP at the NE-lysyl amino group with N-hydroxysuccinimide esters of aminomethylcoumarin (Mec) and biotin (Btn) produced the bifunctional ligands PhAcAL(Mec jVP and PhAcAL(Btn)VP, respectively. Pharmacological characterization of these peptides revealed that all were high-affinity V,,-selective antagonists. PhAcAL(BtnjVP can simultaneously bind to both the rat liver V,, receptor and avidin conjugates. Using this strategy, we were able to study the distribution of V,, receptors on the surface of the rat mammary tumour cell line, WRK-1. Routine epifluorescent microscopy and confocal image analysis were used to observe the distribution of avidin -Texas-Red associated with receptor-bound PhAcAL(Btn)VP. We conclude that PhAcALVP is a useful precursor for the production of hetero-bifunctional V,,-selective ligands. Both PhAcAL-(Mec)VP and PheAcAL(Btn)VP can be used selectively to probe the Vt, receptor and will be versatile tools for a variety of histocytochemical applications, including receptor localization and purification.[Args]vasopressin ([Arg'IVPj, a neurohypophyseal peptide hormone, regulates a plethora of physiological processes in mammals that include well-documented pressor (Hofbauer et al., 1984) and antidiuretic actions (reviewed by Handler and Orloff, 1981). To date, three pharmacologically distinct subtypes of vasopressin receptor (VPR) have been described and classified as Vla, V,, and V, (Michell et al., 1979;Jard et al., 1986). The V1, VPR subtype, expressed by vascular smooth muscle and hepatocytes, has been well characterized and is known to regulate blood pressure and liver function by stimulating phosphoinositidase C (Michell et al., 1979). The V,, VPR is also expressed by other cell types in the central nervous system and periphery (Jard et al., 1987;Maggi et al., 1988;Tribollet et al., 1988). The availability of V,,-selective ligands, particularly antagonists (Manning et al., 1987a), has greatly facilitated studies addressing the nature and function of the V,, VPR subtype. In this regard, the synthetic peptide [l -P-mercaptocyclopentamethylenepropionic acid, 2-O-methyltyrosine, Arg8]vasopressin [d(CH,j,Tyr(Me)2]AVP which is a V,, VPR antagonist (Kruszynski et al., 1980) has proved particularly useful for selectively blocking V,, VPR function. Like [d(CH,),Tyr(Me)2]AVP, the vast majority of potent structural analogues of [Arg8]VP have incorporated an intramolecular disulphide bond between positions 1 and 6 to mimic the cystine bond in [Arg'IVP. Manning and his co-workers (Manning et al., 1984 were also the first to demonstrate that the nature of the amino acid residue at position 9 does not greatly influence the potency of cyclic vasopressin antagonists. Indeed, all that may be required for high-a...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Fluorescent and biotinylated linear peptides as selective bifunctional ligands for the V_1a vasopressin receptor

Howl

Wang

Kirk

et al. 1993

European Journal of Biochemistry

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“…Arginine VP and the VP receptor antagonists were obtained from Bachem (Torrence, CA). The receptor antagonists were selected on the basis of their affinity for the V 1 and/or V2 receptors (24)(25)(26)(27). Peptides were dissolved in sterile 0.9% NaCl.…”

Section: Methodsmentioning

confidence: 99%

“…Peptides were dissolved in sterile 0.9% NaCl. The antagonists were administered in doses of 0 ng (isotonic saline), 10 8,9 ]VP (TVA-AVP), which is one of the most potent V2 receptor antagonists (25,26).…”

Section: Methodsmentioning

confidence: 99%

Brain vasopressin and sodium appetite

Flynn

Kirchner

Clinton

2002

American Journal of Physiology-Regulatory, Integrative and Comp

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ventricular injections of vasopressin (VP) and antagonists with varying degrees of specificity for the VP receptors were used to identify the action of endogenous brain VP on 0.3 M NaCl intake by sodium-deficient rats. Lateral ventricular injections of 100 ng and 1 g VP caused barrel rotations and a dramatic decrease in NaCl intake by sodium-deficient rats and suppressed sucrose intake. 8 ]VP (MeT-AVP) significantly suppressed NaCl intake by sodium-deficient rats without causing motor disturbances. MeT-AVP had no effect on sucrose intake (0.1 M). In contrast, the selective V2 receptor antagonist had no significant effect on NaCl intake. Last, injections of 100 ng MeT-AVP decreased mean arterial blood pressure (MAP), whereas 100 ng VP elevated MAP and pretreatment with MeT-AVP blocked the pressor effect of VP. These results indicate that the effects produced by 100 ng MeT-AVP represent receptor antagonistic activity. These findings suggest that the effect of exogenous VP on salt intake is secondary to motor disruptions and that endogenous brain VP neurotransmission acting at V1 receptors plays a role in the arousal of salt appetite. neurohypophysial peptides; taste; blood pressure; V 1 receptor; V2 receptor VASOPRESSIN (VP) has diverse biological actions and target systems. In addition to the well-known neuroendocrine effects, VP meets the criteria for a brain neurotransmitter. For example, it is synthesized in several brain nuclei, including the paraventricular nucleus of the hypothalamus, medial amygdala, and bed nucleus of the stria terminalis (1, 5). Also, physiological stimuli trigger the release of VP in specific brain regions where it exerts its effects on pre-and postsynaptic membranes (11, 31).VP exerts its effects through receptors that have been divided into two broad classes, the V 1 and V 2 receptors. The V 1 class can be further divided into the V 1a and V 1b receptors (16,17,42). The receptors differ in their distribution and associated second messenger system (17). Neurons that synthesize VP have extensive vasopressinergic projections to sites along the neuraxis, including the septum, hippocampus, amygdala, subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), nucleus of the solitary tract, dorsal motor nucleus of the vagus, and spinal cord (1,29,40). Radioligand receptor autoradiography and in situ hybridization results indicate that VP binding sites are distributed in the brain and that the distribution of these sites often overlaps with the terminal distributions of vasopressinergic neurons (22,32,46).Brain release and pituitary release of VP often parallel one another. For example, systemic osmotic and hypovolemic stimuli that increase circulating VP levels also stimulate the release of VP in the lateral septum and lateral ventricle (4). Manipulations that facilitate salt intake can also stimulate the systemic release of VP. The simultaneous administration of furosemide and a low dose of the angiotensin-converting enzyme captopril arouses a sodium appetite and increases ...

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“…The selective antagonists [deamino-Pen(1), O-Me-Tyr(2), Arg(8)]-vasopressin (V-1880; Lot # 053K13071; Sigma, St Louis, MO, USA) and [adamantaneacetyl(1), O-Et-DTyr(2), Val(4), Aminobuturyl(6), Arg(8,9)]-vasopressin (V-2381; Lot # 073K11151; Sigma, St Louis, MO, USA) were used for inhibition of V 1 and V 2 receptors, respectively (Manning et al, 1987). One hundred or 500 ng of the drugs in 2 mL saline were administered 5 mins after MCAO by intracerebroventricular administration (0.9 mm left, 0.1 mm posterior, and 3.1 mm deep relative to bregma).…”

Section: Application Of V 1 and V 2 Receptor Antagonistsmentioning

confidence: 99%

Role of Arginine Vasopressin V₁ and V₂ Receptors for Brain Damage After Transient Focal Cerebral Ischemia

Vakili

Kataoka

Plesnila

2005

J Cereb Blood Flow Metab

128

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Brain edema formation is one of the most important mechanisms responsible for brain damage after ischemic stroke. Despite considerable efforts, no specific therapy is available yet. Arginine vasopressin (AVP) regulates cerebral water homeostasis and has been involved in brain edema formation. In the current study, we investigated the role of AVP V 1 and V 2 receptors on brain damage, brain edema formation, and functional outcome after transient focal cerebral ischemia, a condition comparable with that of stroke patients undergoing thrombolysis. C57/BL6 mice were subjected to 60-min middle cerebral artery occlusion (MCAO) followed by 23 h of reperfusion. Five minutes after MCAO, 100 or 500 ng of [deamino-Pen(1), O-Me-Tyr(2), Arg (8) .2% in controls; Po0.001), blood-brain barrier disruption by 75% (Po0.001), and functional deficits 24 h after ischemia, while V 2 receptor inhibition had no effect. The current findings indicate that AVP V 1 but not V 2 receptors are involved in the pathophysiology of secondary brain damage after focal cerebral ischemia. Although further studies are needed to clarify the mechanisms of neuroprotection, AVP V 1 receptors seem to be promising targets for the treatment of ischemic stroke.

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No requirement of cyclic conformation of antagonists in binding to vasopressin receptors

Cited by 78 publications

References 13 publications

Fluorescent and biotinylated linear peptides as selective bifunctional ligands for the V_1a vasopressin receptor

Fluorescent and biotinylated linear peptides as selective bifunctional ligands for the V_1a vasopressin receptor

Brain vasopressin and sodium appetite

Role of Arginine Vasopressin V₁ and V₂ Receptors for Brain Damage After Transient Focal Cerebral Ischemia

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No requirement of cyclic conformation of antagonists in binding to vasopressin receptors

Cited by 78 publications

References 13 publications

Fluorescent and biotinylated linear peptides as selective bifunctional ligands for the V1a vasopressin receptor

Fluorescent and biotinylated linear peptides as selective bifunctional ligands for the V1a vasopressin receptor

Brain vasopressin and sodium appetite

Role of Arginine Vasopressin V1 and V2 Receptors for Brain Damage After Transient Focal Cerebral Ischemia

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Product

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Fluorescent and biotinylated linear peptides as selective bifunctional ligands for the V_1a vasopressin receptor

Fluorescent and biotinylated linear peptides as selective bifunctional ligands for the V_1a vasopressin receptor

Role of Arginine Vasopressin V₁ and V₂ Receptors for Brain Damage After Transient Focal Cerebral Ischemia