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1.
Kidney Int ; 49(6): 1530-3, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8743448
2.
Am J Prev Med ; 7(6): 363-73, 1991.
Article in English | MEDLINE | ID: mdl-1790044

ABSTRACT

Sexual assault of women in the United States may have a prevalence rate of 25% or more. Moreover, the majority of survivors of sexual assault know their assailants. Consequences of assault may be severe and long-term, including fear and anxiety, depression, suicide attempts, difficulties with daily functioning and interpersonal relationships, sexual dysfunction, and a whole range of somatic complaints. Recent evidence implicates societal factors, such as acceptance of rape myths, rigid sex role stereotyping beliefs, and acceptance of violence as a legitimate means for obtaining compliance in interpersonal relationships, in the etiology of sexual violence against women. I present a model for primary, secondary, and tertiary prevention of rape. Primary prevention represents a program of anticipatory guidance in a developmental framework. Secondary prevention entails identification of and early intervention in dysfunctional families. Tertiary prevention consists of the appropriate treatment of the survivor of sexual assault to prevent or minimize subsequent physical and psychological problems. This preventive framework may be incorporated into the practice of clinical preventive medicine and primary care.


Subject(s)
Primary Prevention , Rape/prevention & control , Female , Gender Identity , Humans , Legislation as Topic , Marriage , Mental Disorders/etiology , Primary Health Care , Rape/psychology , Rape/statistics & numerical data , Stereotyping , United States , Violence
3.
West J Med ; 152(6): 725-8, 1990 Jun.
Article in English | MEDLINE | ID: mdl-2353489

ABSTRACT

Low birth weight is the major determinant of infant mortality. Continuing declines in infant mortality in the United States are due to the use of neonatal intensive care services; less progress has been made toward preventing low birth weight. I examined how the demographic, socioeconomic, and health services use variables affected rates of low birth weights in Pima County, Arizona, in 1985. Women at greatest risk of having the smallest infants were those younger than 21 years and those with fewer than 6 prenatal visits. Nulliparous women with fewer than 6 prenatal visits showed a still greater risk of having an infant of low birth weight. Women without medical insurance coverage had babies with the lowest mean birth weights, as well as significantly fewer prenatal visits. As the number of uninsured in the United States increases, the effect of lack of insurance among pregnant women becomes increasingly important. To prevent low-weight births, comprehensive maternity care services must be available to all pregnant women regardless of ability to pay.


Subject(s)
Infant Mortality , Infant, Low Birth Weight , Prenatal Care , Adolescent , Adult , Arizona , Data Collection , Demography , Educational Status , Female , Humans , Infant, Newborn , Insurance, Health , Maternal Age , Parity , Risk Factors , Socioeconomic Factors
4.
Int J Pept Protein Res ; 34(5): 353-7, 1989 Nov.
Article in English | MEDLINE | ID: mdl-2613436

ABSTRACT

Solution methods, using N-hydroxysuccinimide esters, were used to synthesize [Glu(NHNH2)4] oxytocin and [Glu(NHNH2)4, Lys8] vasopressin. In these analogs of neurohypophyseal hormones, the side-chain carboxamide function of a glutamine residue is formally replaced by a hydrazide group at position 4. The hormone analogs were assayed for uterototonic activity, milk ejection activity, antidiuretic activity, and rat pressor activity. The specific biological activities of the oxytocin and vasopressin analogs were decreased compared to the respective parent hormones in all assay systems.


Subject(s)
Biological Assay , Lypressin/analogs & derivatives , Oxytocin/analogs & derivatives , Animals , Chromatography, Thin Layer , Female , Glutamates/chemical synthesis , Hydrolysis , In Vitro Techniques , Lypressin/chemical synthesis , Lypressin/pharmacology , Oxytocin/chemical synthesis , Oxytocin/pharmacology , Peptides/chemical synthesis , Rats
5.
Endocrinology ; 121(6): 2245-50, 1987 Dec.
Article in English | MEDLINE | ID: mdl-3119316

ABSTRACT

This study reports the synthesis and biological activities of 1-desamino, 7-lysine-(4-azidobenzoyl), 8-arginine vasotocin (d7-N3-AVT). This compound was found to be biologically active in the rat antidiuretic assay (20 U/mg), to behave as an antagonist of vasopressin in the rat pressor assay (pA2 = 6.6), and to yield a half-maximal hydroosmotic response in the isolated toad urinary bladder at a bath concentration of 2.4 X 10(-8) M. When toad bladders were exposed to d7-N3-AVT in the presence of long wavelength UV light, the hydroosmotic response persisted in spite of prolonged and repeated periods of washout. By contrast, the hydroosmotic response in control bladders after stimulation with d7-N3-AVT in the absence of UV irradiation was fully reversed within 15 min of washout. A membrane preparation derived from bladders that had been photolabeled with d7-N3-AVT and washed for 1 h specifically bound 325 fmol [3H]vasopressin/mg protein. Matched bladders exposed to the analog in the absence of UV irradiation and washed for 1 h specifically bound 591 fmol [3H]vasopressin per mg of protein. These studies indicate that d7-N3-AVT binds covalently to hydroosmotic receptors of toad urinary bladder and forms a complex that is functional in triggering an increase in the permeability to water of the epithelium. This analog may prove useful in the isolation and purification of vasotocin receptors in lower vertebrates.


Subject(s)
Affinity Labels/chemical synthesis , Receptors, Angiotensin/metabolism , Receptors, Vasopressin , Vasotocin/analogs & derivatives , Animals , Bufo marinus , Diuresis/drug effects , Indicators and Reagents , Rats , Rats, Inbred Strains , Receptors, Angiotensin/drug effects , Urinary Bladder/drug effects , Urinary Bladder/physiology , Vasotocin/chemical synthesis , Vasotocin/metabolism , Vasotocin/pharmacology
6.
Int J Pept Protein Res ; 30(5): 577-82, 1987 Nov.
Article in English | MEDLINE | ID: mdl-2830197

ABSTRACT

The present study describes the synthesis and biological activities of the photoreactive vasotocin analog 1-deamino[8-lysine(N epsilon-4-azidobenzoyl)] vasotocin ([Mpa1, Lys(N epsilon-4-azidobenzoyl)8]vasotocin). The analog was obtained by introducing the photoreactive aryl azido group at the epsilon-amino group of Lys8 in [Mpa1, Lys8]-vasotocin, which was synthesized by the solid phase method. In the isolated toad urinary bladder the photoaffinity analog of vasotocin retained hydroosmotic activity in the absence of u.v.-light. After irradiation the osmotic water flow across the bladder wall increased. Moreover, the water permeability remained high during repeated periods of washout, suggesting that the analog formed covalent complexes with vasotocin receptors in the toad bladder. In the rat uterotonic assay the photoreactive vasotocin analog was without photoactivation a mild agonist. These studies suggest that the photoaffinity analog of vasotocin might be useful for the isolation of vasotocin receptors in low vertebrates and oxytocin receptors in mammals.


Subject(s)
Receptors, Angiotensin/metabolism , Receptors, Vasopressin , Vasotocin/analogs & derivatives , Animals , Bufo marinus , Female , Oxytocin , Rats , Receptors, Angiotensin/drug effects , Receptors, Oxytocin , Urinary Bladder/drug effects , Urinary Bladder/metabolism , Vasotocin/chemical synthesis , Vasotocin/pharmacokinetics , Water/metabolism
7.
J Med Chem ; 30(8): 1509-12, 1987 Aug.
Article in English | MEDLINE | ID: mdl-3612693

ABSTRACT

Three arginine-vasopressin (AVP) analogues in which the proline residue in position 7 was substituted with 4-hydroxyproline were synthesized by solid-phase techniques, and their biological activities were evaluated by antidiuretic, pressor, and uterotonic bioassays. The [7-trans-4-hydroxy-L-proline]AVP, the 1-desamino[7-trans-4-hydroxy-L-proline]AVP, and the 1-desamino[7-cis-4-hydroxy-L-proline]AVP analogues showed a high antidiuretic and strikingly high uterine activity, a sharp decrease in pressor activity, and a better antidiuretic and uterine to pressor selectivity than the parent compound, arginine-vasopressin. The uterine activities are the highest so far assayed in AVP analogues with replacements in position 7.


Subject(s)
Arginine Vasopressin/analogs & derivatives , Hydroxyproline , Animals , Arginine Vasopressin/chemical synthesis , Arginine Vasopressin/pharmacology , Diuresis/drug effects , Female , Molecular Conformation , Pressoreceptors/drug effects , Rats , Structure-Activity Relationship , Uterus/drug effects
8.
J Med Chem ; 30(8): 1526-9, 1987 Aug.
Article in English | MEDLINE | ID: mdl-3112398

ABSTRACT

The chemically reactive groups of [8-arginine]vasotocin (AVT) are the alpha-amino group in position 1, the phenolic hydroxyl group of the tyrosyl residue in position 2, and the side-chain functional group of the basic amino acid residue in position 8. Acylation or alkylation of any of these chemically reactive groups yields hormone analogues with sharply diminished biological activities in most assay systems. Since none of the chemically reactive groups in the native AVT (or other neurohypophyseal hormone) sequences is a suitable chemical port for acylation with affinity ligands and reporter groups, we have undertaken the rational design of AVT analogues in which a residue capable of being acylated has been incorporated into points of the AVT structure where structural modifications are expected to have as little effect as possible on biological activity. Empirical structure-activity relationships among neurohypophyseal hormone analogues as well as conformational models in solution and in the crystalline state suggest that positions 4 and 7 are likely points for the introduction of acylation ports. We have previously synthesized an analogue of [1-desamino]AVT (dAVT) with a lysyl residue in position 4 ([4-lysine]dAVT) and demonstrated that acylation of the side chain of this residue yields useful reporter and photoaffinity analogues. We now report the synthesis of the corresponding analogue with a lysyl residue in position 7 ([7-lysine]dAVT), which also yields potent acyl derivatives suitable for affinity ligands and photoaffinity ligands.


Subject(s)
Lysine , Vasotocin/analogs & derivatives , Animals , Blood Pressure/drug effects , Bufo marinus , Chemical Phenomena , Chemistry , Diuresis/drug effects , Osmosis , Rats , Structure-Activity Relationship , Urinary Bladder/drug effects , Urinary Bladder/physiology , Vasotocin/pharmacology
9.
Am J Physiol ; 252(6 Pt 1): C657-62, 1987 Jun.
Article in English | MEDLINE | ID: mdl-3109249

ABSTRACT

A photoreactive analogue of vasotocin, [1-desamino,4-lysine(azidobenzoyl),8-arginine]vasotocin (4-N3-AVT), has been examined in the isolated toad urinary bladder for biological activity and binding to hormonal receptors. Although 4-N3-AVT induced only a small increase in bladder permeability to water, it behaved as a potent inhibitor of hydrosmotic action of [8-arginine]vasotocin (AVT) and [8-arginine]vasopressin (AVP). The inhibitory action of 4-N3-AVT was readily reversed on removal of the analogue from the serosal bathing solution. On the other hand, when bladders were exposed to 4-N3-AVT in the presence of long wavelength UV light (365 nm), the inhibition by 4-N3-AVT was not reversed on washout of the analogue. The dose of vasopressin required for a half-maximal response (ED50 value) was increased from 5 X 10(-9) to 1.3 X 10(-7) M in bladders photolabeled with 4-N3-AVT and the maximal response capacity of the tissue (intrinsic activity) was reduced to 79% of nonphotolabeled controls. A crude membrane preparation derived from bladders photolabeled with 4-N3-AVT contained 72 fmol of specific binding sites for tritium-labeled vasopressin per milligram protein, whereas nonphotolabeled controls had 136 fmol of specific binding sites per milligram protein. These observations suggest that 4-N3-AVT forms a covalent bond with hydrosmotic receptors in the presence of UV light. This is the first antagonistic photoaffinity analogue observed in the toad bladder and it may serve as a useful tool for analyzing the cellular mechanism of action of antidiuretic hormone.


Subject(s)
Receptors, Angiotensin/metabolism , Receptors, Vasopressin , Urinary Bladder/metabolism , Vasotocin/analogs & derivatives , Vasotocin/metabolism , Animals , Arginine Vasopressin/pharmacology , Biological Assay , Bufo marinus , Cell Membrane Permeability , Dose-Response Relationship, Drug , Time Factors , Ultraviolet Rays , Urinary Bladder/radiation effects
11.
Am J Physiol ; 251(3 Pt 1): C443-7, 1986 Sep.
Article in English | MEDLINE | ID: mdl-3019148

ABSTRACT

Toad bladders were exposed to [Phe(p-N3)3]AVP (N3-AVP), an analogue of vasopressin with a photoreactive p-azido group in position three, in the presence and absence of ultraviolet (UV) light. Bladders exposed to the analogue in the presence of UV light showed an increase in membrane permeability to water, which persisted in spite of repeated and prolonged washout of analogue. In contrast, the hydroosmotic response induced by the analogue in the absence of UV light was readily reversed on washout. Aliquots of a broken epithelial cell preparation, derived from bladders that had been exposed to the analogue in the presence of UV light, bound less tritium-labeled vasopressin ([3H]AVP) than control aliquots that had been exposed to the analogue in the absence of UV irradiation or irradiated in the absence of the analogue. Membrane preparations that had not been photolabeled had specific binding sites for [3H]AVP in excess of 1,800 fmol/mg protein without evidence of saturation at a [3H]AVP concentration of 250 nM. Conversely, photolabeled membranes were saturated at a [3H]AVP concentration of 100 nM. The present studies demonstrate that a high proportion of [3H]AVP binding sites can be covalently labeled with N3-AVP and that at least some of these N3-AVP-bound sites are functional in triggering an increase in membrane permeability to water.


Subject(s)
Arginine Vasopressin/analogs & derivatives , Azides/metabolism , Receptors, Angiotensin/metabolism , Receptors, Cell Surface/metabolism , Urinary Bladder/metabolism , Affinity Labels/metabolism , Animals , Arginine Vasopressin/metabolism , Bufo marinus , Cell Membrane/metabolism , Cell Membrane Permeability/drug effects , Epithelium/metabolism , Female , Kinetics , Photochemistry , Receptors, Vasopressin , Ultraviolet Rays , Water/metabolism
12.
Int J Pept Protein Res ; 28(2): 154-62, 1986 Aug.
Article in English | MEDLINE | ID: mdl-3771100

ABSTRACT

Tocinoic acid analogs with penicillamine in place of one or both of the cysteine residues have been studied and [1-beta-mercaptopropionic acid, 6-penicillamine] tocinoic acid (dPen6TA) and [1-beta,beta-dimethyl-beta-mercaptopropionic acid, 6-penicillamine] tocinoic acid (dPen1Pen6TA) have been synthesized in solution. Biological activities of these 2 compounds and those of the previously synthesized [1-beta,beta-dimethyl-beta-mercaptopropionic acid] tocinoic acid (dPen1TA) have been assayed. It was found that dPen1TA and dPen1Pen6TA, both of which have a beta,beta-dimethyl-beta-mercaptopropionic acid in position 1, are strong inhibitors of the uterine activity of oxytocin in vitro (without Mg2+) with pA2 values of 7.1 and 7.8, respectively, whereas dPen6TA with penicillamine in position 6 is a mild agonist.


Subject(s)
Oxytocin/analogs & derivatives , Oxytocin/pharmacology , Amino Acid Sequence , Animals , Chemical Phenomena , Chemistry , Female , Indicators and Reagents , Oxytocin/chemical synthesis , Structure-Activity Relationship , Uterine Contraction/drug effects
13.
Int J Pept Protein Res ; 27(6): 679-84, 1986 Jun.
Article in English | MEDLINE | ID: mdl-3759339

ABSTRACT

We have synthesized three oxytocin analogs containing an oxygen atom in the amino acid side chain in position 3 to determine the influences of increased side chain length and of hydrophilicity on the potencies and specificities of the resulting analogs. These three analogs: [3-O-methylhomoserine] oxytocin, [3-O-ethylserine] oxytocin, and [3-O-methylthreonine] oxytocin - have the following activities in U/mg: 490, 208, 265, milk ejection; 125, 129, 63, uterus in vivo; 0.2, 16, 0.03, antidiuretic; and 0.1, 0.5, 0.1, pressor. The results show that a longer side chain, [3-O-methylhomoserine] and [3-O-ethylserine] vs. [3-O-methylthreonine], tends to increase all activities. Moving the hydrophilic oxygen farther away from the peptide backbone, on the other hand, decreases vasopressin-like activities but increases or has no effect on oxytocin-like activities.


Subject(s)
Oxytocin/analogs & derivatives , Oxytocin/chemical synthesis , Animals , Diuresis/drug effects , Female , In Vitro Techniques , Indicators and Reagents , Milk Ejection/drug effects , Oxytocin/pharmacology , Phenoxybenzamine/pharmacology , Pregnancy , Rats , Structure-Activity Relationship , Uterine Contraction/drug effects , Vasoconstriction/drug effects
14.
Endocrinology ; 118(3): 1026-31, 1986 Mar.
Article in English | MEDLINE | ID: mdl-2936596

ABSTRACT

The synthesis of the photoreactive neurohypophyseal hormone analog [3-(p-azidophenylalanine]arginine vasopressin [( Phe(p-N3)3]AVP is described. [Phe(p-N3)3]AVP exhibits a rat antidiuretic activity of 173 +/- 18 U/mg and a high binding affinity for the renal V2 vasopressin receptor in bovine kidney; an apparent dissociation constant KD of (1.3 +/- 0.2) X 10(-8) M was determined. In the toad bladder [Phe(p-N3)3]AVP was the most potent photoreactive vasopressin analog studied to date. It stimulated urea transport to the same maximal value as AVP with an ED50 of (3.1 +/- 0.7) X 10(-8) M. After irradiation with UV light, [Phe(p-N3)3]AVP bound irreversibly to toad bladder receptors and generated a persistent increase in bladder permeability to urea and to water. Analogs of 1-deamino-vasopressin with a photoreactive aryl azido group either in position 4 or 8 of the vasopressin sequence retain substantial rat antidiuretic activity. Compounds with a photoreactive group in position 8 showed a low activity in the isolated toad bladder in the dark; but on exposure to UV light, the activity of these analogs increased both with respect to urea and water transport, and the permeability response persisted during prolonged periods of washout. These studies provide evidence that analogs of vasopressin with an azido moiety in position 3 or 8 bind covalently to toad bladder receptors and produce an irreversible stimulation of transport processes.


Subject(s)
Arginine Vasopressin/analogs & derivatives , Water-Electrolyte Balance/drug effects , Animals , Arginine Vasopressin/pharmacology , Biological Transport/drug effects , Blood Pressure/drug effects , Bufo marinus , Cattle , Epithelium/metabolism , Female , In Vitro Techniques , Kidney Medulla/physiology , Permeability , Photochemistry , Receptors, Angiotensin/metabolism , Receptors, Vasopressin , Urea/metabolism , Urinary Bladder/physiology , Water/metabolism
15.
Am J Physiol ; 249(1 Pt 1): C84-8, 1985 Jul.
Article in English | MEDLINE | ID: mdl-3160246

ABSTRACT

The effects of a photoaffinity label for arginine vasopressin receptors, [Phe2, Phe(p-N3)3]AVP (N3-AVP), on urea permeability and adenylate cyclase activity have been investigated in the toad urinary bladder. This compound, when activated by ultraviolet light, induced a maximal and persistent increase in the urea permeability of the intact bladder and a persistent increase in the adenylate cyclase activity of toad bladder epithelial cell homogenates. Covalent attachment of the analogue to target tissue during photolysis was equivalent at 4 and 20 degrees C. Bladders exposed to N3-AVP in the presence of AVP during photolysis were substantially less permeable to urea than controls that had been exposed to N3-AVP alone. These findings constitute further evidence in support of our previous suggestion that N3-AVP binds covalently to AVP receptors and, in addition, demonstrates that N3-AVP evokes a persistent increase in adenylate cyclase activity which, in turn, triggers a persistent increase in bladder permeability to urea.


Subject(s)
Adenylyl Cyclases/metabolism , Affinity Labels/pharmacology , Arginine Vasopressin/analogs & derivatives , Urea/metabolism , Urinary Bladder/drug effects , Animals , Arginine Vasopressin/pharmacology , Biological Transport/drug effects , Bufo marinus , Female , In Vitro Techniques , Permeability , Photochemistry , Receptors, Angiotensin/metabolism , Receptors, Vasopressin , Temperature , Ultraviolet Rays , Urinary Bladder/metabolism
16.
Endocrinology ; 117(1): 196-200, 1985 Jul.
Article in English | MEDLINE | ID: mdl-3924578

ABSTRACT

The present study describes the synthesis and biological activities of a vasopressin (VP) analog which binds covalently to receptors via a photoreactive p-azido group in position 3 and which contains a rhodamine label in position 8 for localization of hormone-receptor complexes by image-intensified fluorescence microscopy. 1-Deamino[3-(p-azidophenylalanine)]-N epsilon-rhodamyllysine-VP (Rhod-N3-dLVP) was obtained in a two-step procedure from the precursor 1-deamino[3(p-aminophenylalanine)]-LVP which was synthesized by a solid phase technique. The rat antidiuretic activity of this compound was 0.34 +/- 0.3 U/mg. Although both Rhod-N3-dLVP and its congener without a rhodamine label, N3-dLVP, did not have any hydroosmotic activity in the isolated toad urinary bladder in the absence of UV light, after UV irradiation they increased both urea and water transport across the bladder wall. Moreover, these permeability effects of Rhod-N3-dLVP persisted during prolonged and repeated periods of washout, suggesting that the photoproducts of this analog had formed covalent complexes with toad bladder receptors. Binding of Rhod-N3-dLVP was inhibited when photolysis was carried out in the presence of 1-deamino-LVP. These studies suggest that Rhod-N3-dLVP has the requisite biological properties to serve as a tool for the localization by fluorescence microscopy of VP receptors in various target tissues.


Subject(s)
Azides/chemical synthesis , Lypressin/analogs & derivatives , Vasopressins , Affinity Labels/chemical synthesis , Animals , Azides/pharmacology , Azides/radiation effects , Biological Assay , Bufo marinus , Cell Membrane Permeability/drug effects , Chemical Phenomena , Chemistry , Diuresis/drug effects , Female , Fluorescent Dyes , Lypressin/chemical synthesis , Lypressin/pharmacology , Lypressin/radiation effects , Methods , Rats , Rhodamines , Ultraviolet Rays , Urea/metabolism , Urinary Bladder/metabolism , Water/metabolism
17.
Biol Cell ; 55(3): 231-7, 1985.
Article in English | MEDLINE | ID: mdl-2939910

ABSTRACT

A series of analogs of vasopressin with photoreactive groups in positions 1, 2, 3, 4, 8 or 9 of the nonapeptide sequence have been studied for their effects on water and urea permeability of the isolated toad urinary bladder. Compounds with photoreactive groups in positions 3 or 8 bound covalently to receptors as judged by a persistent increase in water and urea permeability following UV irradiation, prevention of photolabeling by incubation in the presence of vasopressin, and a persistent increase in membrane-bound adenylate cyclase activity. Some analogs were inactive in the dark, but became active and bound covalently to receptors during photolysis. Other analogs were inhibitors or agonists in the dark, but did not bind to receptors following UV irradiation. Time course studies with photolabelled bladders showed a stable urea flux for 4 hr in the absence of osmotic water flow. However, in the presence of water flow urea flux was initially enhanced (solvent drag effect) and later retarded (diminished urea permeability). Binding of photoaffinity analogs to receptors was not diminished with acidification of the serosal bathing medium, lowering of the bath temperature from 21 degrees C to 4 degrees C or with addition of prostaglandin E1. However, the capacity of photoreactive analogs to effect an increase in transmural water flux, once the analog was bound covalently to receptors, was markedly diminished under these conditions.


Subject(s)
Urinary Bladder/drug effects , Vasopressins/pharmacology , Adenylyl Cyclases/metabolism , Affinity Labels/metabolism , Animals , Body Water/metabolism , Bufo marinus , In Vitro Techniques , Kinetics , Osmosis/drug effects , Permeability , Receptors, Angiotensin/drug effects , Receptors, Angiotensin/metabolism , Receptors, Vasopressin , Structure-Activity Relationship , Ultraviolet Rays , Urea/metabolism , Urinary Bladder/metabolism
18.
Int J Pept Protein Res ; 23(5): 551-7, 1984 May.
Article in English | MEDLINE | ID: mdl-6547408

ABSTRACT

Analogs of arginine vasopressin (AVP) and lysine vasopressin (LVP)--with an L-alaninamide residue or a D-alaninamide residue replacing the naturally occurring glycinamide in position 9--lose virtually all pressor activity but retain from 10 to 70% of the antidiuretic activity of their parent hormones. These findings, in conjunction with the data of others on the biological consequences of alterations in positions 7 and 8, show that the antidiuretic receptor will tolerate considerably more structural alteration in the C-terminal tripeptide "tail" of the vasopressins than will the pressor receptor.


Subject(s)
Arginine Vasopressin/analogs & derivatives , Diuresis/drug effects , Lypressin/analogs & derivatives , Vasoconstrictor Agents/chemical synthesis , Animals , Arginine Vasopressin/chemical synthesis , Arginine Vasopressin/pharmacology , Biological Assay , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Indicators and Reagents , Lypressin/chemical synthesis , Lypressin/pharmacology , Rats , Structure-Activity Relationship , Vasoconstriction/drug effects
19.
Am J Physiol ; 246(5 Pt 1): C486-93, 1984 May.
Article in English | MEDLINE | ID: mdl-6326607

ABSTRACT

We have shown previously ( Eggena et al., Endocrinology 113: 1413-1421, 1983) that [Phe2,Phe(p-N3)3]-AVP induces a prolonged hydrosmotic response in the toad bladder when activated by ultraviolet (UV) light. To determine whether this response is due to covalent binding of the ligand with 8-arginine vasopressin (AVP) receptors, bladders were challenged with the ligand in the presence of AVP or the AVP antagonist, [Phe(p-N3)2]AVP, during photolysis. The permeability of bladders to water was tested subsequently in the absence of hormone or analogue. Bladders with a history of exposure to AVP (or to [Phe-(p-N3)2]AVP) during UV irradiation were considerably less permeable to water than controls, suggesting that [Phe2,Phe(p-N3)3]AVP, AVP, and [Phe(p-N3)2]AVP compete for the same receptor system during photolysis. Other experiments were directed at defining optimal conditions for covalent linkage of [Phe2,Phe(p-N3)3]AVP to receptors. These studies have indicated that two 10-min cycles of UV irradiation are more effective than one and that osmotic water flow at a rate of 1 mg X min-1 X cm-2 during irradiation does not interfere with the ligand-receptor interaction. Acidification of the serosal bath solution to pH 6.5 did not inhibit covalent binding of the ligand to receptors during photolysis. However, the capacity of the ligand-receptor complex to increase bladder permeability to water was markedly inhibited by serosal fluid acidification. These experiments have suggested that [Phe2 ,Phe(p-N3)3]AVP binds covalently to AVP receptors during photolysis and generates a signal that gradually decays as a function of time.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Arginine Vasopressin/analogs & derivatives , Receptors, Cell Surface/metabolism , Urinary Bladder/physiology , Vasopressins/metabolism , Animals , Arginine Vasopressin/metabolism , Arginine Vasopressin/pharmacology , Bufo marinus , Female , Kinetics , Photolysis , Receptors, Vasopressin , Ultraviolet Rays , Urinary Bladder/drug effects , Urinary Bladder/radiation effects
20.
Int J Pept Protein Res ; 23(1): 78-83, 1984 Jan.
Article in English | MEDLINE | ID: mdl-6199318

ABSTRACT

Substituting sarcosine or N-methylalanine for proline in the inhibitory vasopressin analogs dPAVP and d(CH2)5AVP had the following effects: 1) milk ejection and antidiuretic activities were severely depressed, 2) pressor antagonism was maintained but weakened somewhat, and 3) antagonism in the uterus in vitro was maintained, but no consistent pattern was seen.


Subject(s)
Alanine/analogs & derivatives , Arginine Vasopressin/analogs & derivatives , Sarcosine , Vasopressins/chemical synthesis , Animals , Arginine Vasopressin/pharmacology , Biological Assay , Drug Antagonism , Female , Indicators and Reagents , Milk Ejection/drug effects , Phenoxybenzamine/pharmacology , Pregnancy , Rats , Structure-Activity Relationship , Uterine Contraction/drug effects
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