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Biomedical subjects

G J Moore

Publications and source records attributed to G J Moore.

At least 91 records · Page 5Linked to original sources
PubMed1989

Angiotensin 'antipeptides': (-)messenger RNA complementary to human angiotensin II (+)messenger RNA encodes an angiotensin receptor antagonist.

(-)mRNA complementary to human angiotensin II (+)mRNA encodes the 'antipeptide' Glu-Gly-Val-Tyr-Val-His-Pro-Val which is structurally related to angiotensin II. Angiotensin II 'antipeptide' (antiANG II) and the desglutamyl heptapeptide (antiANG III) are Type I antagonists which inhibit the contractile action of angiotensin at smooth muscle receptors by binding to a negative modulatory site on the angiotensin receptor which is distinct from the angiotensin binding site. These findings may illustrate that the inhibitory binding site on the angiotensin receptor exists to accomodate a naturally occurring inhibitor(s), which is encoded by the DNA strand complementary to that encoding angiotensin II.

Amino Acid Sequence↗
PubMed1989

Inhibition of oxytocin-induced but not angiotensin-induced rat uterine contractions following exposure to sodium sulfide.

Low concentrations (0.15-15 microM) of sodium sulfide reversibly attenuated the contractile response of the isolated rat uterus to oxytocin without affecting angiotensin II responsiveness. These findings suggest that functionally important disulfide bonds in the rat uterine oxytocin receptor, but not the angiotensin receptor, are sensitive to hydrosulfide ion. Reduction of oxytocin receptors by hydrosulfide ion may be a mechanism by which low levels of H2S delay parturition in rats.

Angiotensin II↗
PubMed1989

Methods for analyzing and interpreting cooperativity in dose-response curves--I. Antagonist effects on angiotensin receptors in smooth muscle.

1. Dose-response curves for angiotensins II and III in the rat isolated uterus, portal vein and aorta, in the absence and presence of the antagonist [Sar1Ile8]ANG II, have been analyzed by methods which detect cooperativity. 2. Hanes-Woolf transformations of dose-response data were used to define phases of positive homotropic cooperativity, and this information was applied to the interpretation of Hill plots. 3. The level of positive cooperativity was found to be higher for ANG II (nH = 1.35-2.00) than ANG III (nH = 1.02-1.43) in the three tissues studied. 4. In the presence of the antagonist [Sar1Ile8]ANG II a decrease in the level of cooperativity produced by both agonists was observed, and high concentrations of the antagonist could induce negative cooperativity. 5. These findings have been interpreted on the basis of a 2-site agonist binding mechanism involving receptor dimers, in which angiotensin agonists induce an increase in their own receptor binding affinity, whereas the antagonist [Sar1Ile8]ANG II decreases the affinity of angiotensin receptors for ANG II and ANG III.

Angiotensin II↗
PubMed1989

Methods for analyzing and interpreting cooperativity in dose-response curves--II. Partial agonists acting on muscarinic receptors in smooth muscle.

1. Dose-response curves for eight muscarinic agonists contracting guinea pig ileum were transformed into Hanes-Woolf plots and Hill plots respectively. 2. Hill plots for three full agonists were linear with slopes of 1.6, illustrating positive homotropic cooperativity involving two or more agonist binding sites. 3. Five partial agonists gave curved Hill plots with Hill coefficients of 1.2-1.7 at low agonist concentration and Hill coefficients of 0.3-0.5 at high agonist concentrations. 4. Hanes-Woolf transformations were used to delineate the transition from positive to negative cooperativity and to assist in the interpolation of Hill plots. 5. The results show that all of the agonists studied induce positive cooperativity, and that the difference between full agonists and partial agonists results from the ability of the latter to induce pronounced negative cooperativity at higher concentrations.

Animals↗
PubMed1989

Response to and control of destructive energy by magnetic resonance.

Magnetic resonance imaging techniques can be used to control and monitor the deposition of destructive energy. The authors evaluated the feasibility of phosphorus-31 magnetic resonance spectroscopy for the control, monitoring, and prediction of the three-dimensional extent of tissue destruction during interstitial laser surgery. Characteristic metabolic changes were demonstrated within the lesion and in the adjacent normal tissue during the deposition of thermal energy.

Adenosine Triphosphate↗
PubMed1988

Calculation of the magnitude and orientation of electrostatic interactions between small aromatic rings in peptides and proteins: implications for angiotensin II.

Electrostatic interactions between aromatic rings are believed to contribute to the intramolecular structuring and biological function of peptides and proteins. The modes of interaction of benzene with 1) benzene (Phe:Phe), 2) imidazole (Phe:His), and 3) imidazole anion (Phe:His), were calculated using all-electron ab initio wavefunctions. In all cases parallel-plate stackings were found to be purely repulsive, whereas perpendicular-plate geometries were attractive with interaction energies of -0.82 (Phe:Phe), -1.19 (Phe:His) and -3.39 (Phe:His) kcal/mole. These data show that small ring interactions in peptides and proteins will prefer perpendicular-plate geometry. For the proposed His:Phe interaction in angiotensin II, the attraction will be three times greater when the imidazole ring carries a negative charge.

Angiotensin II↗
PubMed1988

[Sar1Ile7]angiotensin III, a new selective antagonist of the pressor effect of angiotensin III in conscious rats.

Two analogues of angiotensin III were compared as antagonists of the pressor response to angiotensin II (ANG II) and angiotensin III (ANG III) in conscious, unrestrained rats. Dose-mean arterial pressure (MAP) response curves were obtained for ANG II and ANG III in the absence or presence of [Ile7]ANG III (1.3 x 10(-7) mol/kg) or [Sar1 Ile7]ANG III (1.2 x 10(-7) mol/kg). In the presence of [Ile7]ANG III, the dose-MAP response curves for ANG II and ANG III were significantly displaced to the right. [Ile7]ANG III behaved as a partial agonist on ANG II but not ANG III receptors. In the presence of [Sar1 Ile7]ANG III, the dose-MAP response curve for ANG III but not ANG II was significantly displaced to the right. This suggests that [Sar1 Ile7]ANG III is a selective antagonist of ANG III in the vasculature. [Ile7]ANG III, on the other hand, antagonizes both ANG II and ANG III receptors. Our results support the hypothesis of the existence of a sub-class of angiotensin receptors activated by ANG III in the vascular smooth muscle.

Angiotensin II↗
PubMed1988

Classification of angiotensin receptors in rat isolated uterus, portal vein, and aorta using a slowly dissociating antagonist [Sar1,Ile8]ANG II for receptor blockade.

Receptor blockade with the slowly dissociating angiotensin (ANG) antagonist, [Sar1,Ile8]ANG II, was used to determine dissociation constants (Kd) for angiotensins II and III at receptors in rat isolated uterus, portal vein and aorta. The Kd values obtained were 1) ANG II: uterus, 2.2 +/- 1.2 X 10(-8)M; portal vein, 8.5 +/- 2.5 X 10(-9)M; aorta, 7.8 +/- 1.7 X 10(-9)M; and 2) ANG III: uterus, 5.7 +/- 1.7 X 10(-7)M; portal vein, 4.5 +/- 3.1 X 10(-7)M; aorta, 1.4 +/- 0.5 X 10(-7)M. For either ANG II or ANG III, there were no clearly significant differences in the Kd values obtained for the smooth muscle tissues investigated. The derived Kd values provided a relationship between receptor occupancy and response that illustrated that the two peptides had similar efficacies in all three tissues. The method provides a quantitative description of receptors and suggests that the angiotensin receptor is of the same type in all three tissues.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1988

Importance of the N-terminal domain of the type II angiotensin antagonist sarmesin for receptor blockade.

Analogues of the competitive angiotensin antagonist [Sar1,Tyr(ME)4]angiotensin II (sarmesin) with modifications at the N-terminus have been prepared by the solid-phase method and purified by reversed-phase HPLC. Substitution of the Sar1 residue of sarmesin with N,N-dimethyl-Gly, N-ethyl-Gly, aminoisobutyric, (methylamino)isobutyric, aminocaproic, and oxamic acids gave analogues that had the following respective antagonist activities (pA2) in the rat isolated uterus assay: less than 6, 6.9, 5.5, 6.0, less than 6, and 5.3. The additional substitution of Ile for Phe at the C-terminus of the latter four peptides gave pA2 values of 7.1, 5.1, less than 5, and 5. Substitution of the Arg2 residue of sarmesin with Nle or Sar abolished antagonist activity. These data emphasize the stringent and discriminating structural requirements in the N-terminal domain of sarmesin that endow this analogue with its antagonist properties and suggest the presence of defined steric constraints in this region of the molecule during receptor blockade.

Angiotensin II↗
PubMed1988

Classification of angiotensin receptors in rat isolated uterus, portal vein, and aorta with the novel competitive antagonist sarmesin.

Blockade of in vitro contractile responses to angiotensins II and III by the reversible competitive angiotensin antagonist [Sar1, Tyr(Me)4]ANG II (sarmesin) was investigated in 3 rat smooth muscle tissues. The pA2 values for sarmesin were: rat uterus, 7.46 +/- 0.04 versus ANG II and 7.46 +/- 0.07 versus ANG III; rat aorta, 7.98 +/- 0.07 versus ANG II and 7.67 +/- 0.08 versus ANG III; rat portal vein, 7.75 +/- 0.05 versus ANG II and 7.41 +/- 0.08 versus ANG III. Statistical analysis revealed that the pA2 values in each tissue were not significantly different, suggesting that ANG II and ANG III interact with the same receptors in each tissue. This conclusion was supported by cross-tachyphylaxis studies. Further statistical analysis revealed that pA2 values were not significantly different between tissues, suggesting that there are no readily discernible differences between angiotensin receptors in the 3 smooth muscle preparations investigated.

Angiotensin II↗
PubMed1987

Angiotensin receptors in resting smooth muscle are the low affinity sites observed in binding studies.

Angiotensin receptors in rat uterine smooth muscle have been investigated by [125I]angiotensin II binding studies in membrane preparations. Scatchard analysis of binding data has demonstrated the presence of low and high affinity angiotensin binding sites with KLD = 3.0 X 10(-8) and KHD = 5.0 X 10(-10)M respectively. These values are identical to our previously reported values for the EC50 and dissociation constant, respectively, obtained from bioassays on intact uterine tissues. The antagonist [Sar1, Ile8]angiotensin II also demonstrates a binding affinity in uterine membranes (pKD = 8.7) which is not significantly different from its apparent binding affinity (pA2 = 8.6) in responding tissues. Taken in conjunction with our previously published bioassay data the present binding studies suggest that the resting state of the angiotensin receptor in smooth muscle is a low affinity state, and that interaction with ANG II induces a portion of the receptors into a high affinity "excited" state. The antagonist [Sar1, Ile8]angiotensin II apparently binds with higher affinity than angiotensin II to the low affinity (resting) state of the receptor.

Angiotensin II↗
PubMed1987

Mechanistic consequences of charge transfer systems in serine proteases and angiotensin: semiempirical computations.

Structures and relative energies for the triads of interacting groups in the serine charge relay system of serine proteases and the proposed tyrosine charge relay system of angiotensin II, respectively, were computed according to the standard MNDOC procedure. The most stable configuration obtained for both systems was one in which the histidine residue was negatively charged. These findings indicate that the histidine ring and not the serine hydroxyl group at the active site of serine proteases would be the nucleophilic center which is acylated by substrate. Similarly, the extreme nucleophilicity of the imidazole anion produced by the proposed triad of interacting groups in angiotensin could provoke the formation of a transient covalent bond (acyl intermediate) between receptor and peptide in the receptor activation mechanism.

Angiotensin II↗