Importance of amino acids on vasopressin-stimulated water flow (original) (raw)
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Journal of Clinical Investigation, 1990
Studies in vitro have shown that L-histidine increases the hydroosmotic response to vasopressin. We examined whether this phenomenon occurs also in vivo. Homozygous Brattleboro rats (di/di) were fed a regular diet (0.5% histidine) or a diet enriched with histidine and received 1 ng of 1-deamino-8->-arginine vasopressin (dDAVP) daily. Addition of histidine (1% by weight) increased post-dDAVP urine osmolality to a level higher than that of control (502±62 vs. 316±36 mosmol/kg, P < 0.05). Similar results were seen with 3.0% and 5.5% dietary histidine. There were significant increases in free-water reabsorption and in the ratio of free-water reabsorption to osmolar clearance, but no difference in osmolal clearance. No significant effect was found with supplemental histidine of 0.5% or less. The cause for these findings appears not to be the metabolism of histidine, since the nonmetabolizable D-histidine had a significant, albeit smaller, effect, and the isonitrogenous addition of albumin, alanine, arginine, or glutamine was ineffective. In part, histidine may operate by increasing cAMP since the renal cAMP content in response to vasopressin is increased in histidine-fed rats (13.1±0.9 vs. 9.8±0.8 nmol/g dry weight, P < 0.01). The role of prostaglandins appears less clear. Histidine greatly decreased urinary PGE2 during baseline (1.5±03 vs. 7.0±2.3 ,g/mg creatinine, P < 0.001), but it profoundly augmented urinary prostaglandin excretion after dDAVP stimulation (40.0±4.2 vs. 7.0±2.0 ,g/mg creatinine, P < 0.001).
General Physiology and Biophysics
Vasopressin and its synthetic analogs were studied for their effect on transepithehal water flux m frog urinary bladder As compared with AVP, 1deamino-8-D-argimne vasopressin (dDAVP) was about 40 times less effective in stimulating osmotic water flow The vasopressin analogs obtained by modification in positions 1 and 2 were [l-(l-mercapto-4-tert-butylcyclohexaneacetic acid)] AVP (I), [l-(l-mercapto-4 methylcyclohexaneacetic acid)]AVP (II), [1-(1mercapto-4-methylcyclohexaneacetic acid)-2-0-methyltyrosine]AVP (III), and those modified m position 4 were [l-(l-mercaptocyclohexaneacetic acid)-4-arginine] AVP (IV), [l-(2-mercaptopropiomc acid)-4-arginine]AVP (V) Any of the above analogs did not influence basal, but antagonized vasopressin-stimulated water flux N-terminallv extended analogs of AVP Ala-AVP (VI), Ser-Ala-AVP (VII) and Thr-Ser-Ala-AVP (VIII) stimulated osmotic water flux to the same extent in concentration 200 times higher as that of AVP We conclude from these studies that vasopressin analogs (I-V) competitively antagonize vasopressin-stimulated hydroosmotic activity in frog urinary bladder probably at the epithelial vasotocin Vi and/or V2 receptor site N-terminal extension of the vasopressin molecule did not influence the capacity of AVP to induce V2 receptor-mediated action, even when used at higher concentrations
Journal of Peptide Science, 1999
We report the solid-phase synthesis and some pharmacological properties of 23 new analogs of arginine vasopressin (AVP) which have the Phe 3 residue replaced by a broad variety of amino acids. Peptides 1 -9 have at position 3: (1) the mixed aromatic/aliphatic amino acid thienylalanine (Thi) and the aliphatic amino acids; (2) cyclohexylalanine (Cha); (3) norleucine (Nle); (4) Leu; (5) norvaline (Nva); (6) Val; (7) alpha-aminobutyric acid (Abu); (8) Ala; (9) Gly. Peptides 10 -23 have at position 3: the aromatic amino acids, (10) homophenylalanine (Hphe); (11) Tyr; (12) Trp; (13) 2-naphthylalanine (2-Nal); the conformationally-restricted amino acids Pro; (15) 2-aminotetraline-2-carboxylic acid (Atc); the polar amino acids (16) Ser; (17) Thr; (18) Gln; and the charged amino acids (19) Asp; (20) Glu; (21) Arg; (22) Lys; (23) Orn. All 23 new peptides were evaluated for agonistic and, where appropriate, antagonistic activities in in vivo antidiuretic (V 2 -receptor) and vasopressor (V 1a -receptor) assays and in in vitro (no Mg 2 + ) oxytocic assays. The corresponding potencies (units/mg) in these assays for AVP are: 323 916; 36996 and 13.990.5. Peptides 1-9 exhibit the following potencies (units/mg) in these three assays: (1) 379914; 36099; 36.291.9; (2) 294921; 73.4 9 2.7; 0.33 9 0.02; (3) 249 9 28; 84.6 9 4.3; 4.72 90.16; (4) 229 919; 21.4 90.6; 2.1 90.2; (5) 13495; 31.2 9 0.9; 28.4 9 0.2; (6) 114 9 9; 45.3 9 2.3; 11.3 91.6; (7) 86.7 9 2.5; 4.29 90.13; 0.45 9 0.03; (8) 15.5 9 1.5; 0.16 9 0.01; 0.02; (9) 3.76 9 0.03; B0.02; in vitro oxytocic agonism was not detected. These data show that the aliphatic amino acids Cha, Nle, Leu, Nva and Val are well-tolerated at position 3 in AVP with retention of surprisingly high levels of antidiuretic activity. Peptides 2 -9 exhibit significant gains in both antidiuretic/vasopressor (A/P) and antidiuretic/oxytocic (A/O) selectivities relative to AVP.
Molecular Physiology of Water Balance
T he hypothalamic-neurohypophyseal-renal axis normally maintains water balance during variations in water intake and nonrenal losses of water. Failure of this mechanism is common in hospitalized patients, and it results in a variety of water-balance disorders. In this article, we begin by reviewing the classic, integrative principles of water balance in mammals and then use this classic model as a framework to discuss the genes and gene products (proteins) involved in water balance. In so doing, our goal is to provide clinicians with a mechanistic basis for decisions regarding the diagnosis and treatment of waterbalance disorders.
pH-Dependent Interactions between Membrane and Histidine-containing Peptides
Chemistry Letters, 2012
A 26-residue peptide containing six histidine (H) residues showed a pH-dependent interaction with a membrane. At a basic pH, where the H residues were deprotonated, the peptides formed a helical structure and adopted a transmembrane alignment in the lipid vesicles. At an acidic pH, where the H residues were protonated, they exhibited a mixture of ¢ and random forms and were aggregated or dissolved in the aqueous phase.
Surface hydrophobicity and water transport of the toad urinary bladder: Effects of vasopressin
The Journal of Membrane Biology, 1988
The present study investigated whether the hydrophobic properties (wettability) of the luminal surface of the toad urinary bladder might play a role in modulating water transport across this epithelium. In the absence of vasopressin (ADH), water transport across the tissue was low, while luminal surface hydrophobicity (water contact angle) was relatively high. Following stimulation by ADH, water transport increased and surface hydrophobicity decreased. The addition of indomethacin to inhibit ADH-induced prostaglandin synthesis did not reduce these actions of ADH. In an attempt to alter water transport in this tissue, a liposomal suspension of surface-active phospholipids was administered to the luminal surface. This addition had no detectable influence on the low basal rates of water transport, but blocked the ADH-induced stimulation of water transport. We suggest that surface-active phospholipids on the toad bladder luminal membrane may contribute to the hydrophobic characteristics of this tissue. ADH may act to decrease surface hydrophobicity, facilitating the movement of water molecules across an otherwise impermeable epithelium. This surface alteration may be associated with the appearance of water channels in the apical membrane.