Augmentation of Aortic Ring Contractions by Angiotensin II Antisense Peptide

Abstract

Abstract-Previous biochemical experiments have revealed two antisense peptide antagonists to human angiotensin II (Ang II), one encoded in the cDNA in the antiparallel reading, the other in the parallel reading. Neither peptide's ability to produce physiological antagonism has been demonstrated previously. Both peptides were tested for their ability to antagonize Ang II-induced contractions on rabbit aorta smooth muscle. Neither peptide had any direct contractile activity. The antiparallel Ang II peptide had physiological antagonism to Ang II contractions at a lower sensitivity than reported in biochemical studies, and its antagonist activity was partially blocked by Ang II antiserum, suggesting that it is not an antipeptide but an Ang II homologue. The parallel Ang II antipeptide also required high concentrations for physiological inhibition. Its contractile inhibition was not affected by Ang II antiserum and diminished the Ang II contraction at high micromolar concentrations, findings consistent with physicochemical data showing that it is an Ang II complement. The concentration of either peptide required to produce an antagonistic physiological effect was too high to predict any pharmacological usefulness. The parallel antipeptide, however, significantly increased the force of muscle contractions at high nanomolar concentrations, thus displaying a unique dual augmentation/antagonist activity. This antipeptide seems to have highly sequence-specific activity because other similar parallel antipeptides had no activity. The parallel antipeptide augmentation mimics the shift in the Ang II dose-response curve produced in hypertension studies of the slow pressor effect of Ang II and may be useful in deducing the currently unknown cause of the slow pressor effect. It may also have some uses in migraine studies. (Hypertension. 1998;31:854-860.)

Hydropathic Complementarity Determines Interaction of Epitope 869HITDTNNK876 in Manduca sexta Bt-R1 Receptor with Loop 2 of Domain II ofBacillus thuringiensis Cry1A Toxins

“…2A). There are other examples of anti-peptides that have similar binding properties as the coded amino acid sequence in the literature (35,51). The analysis of hydropathic profiles of the coding and noncoding scFv73 CDR3 amino acid sequences revealed that they share a similar hydropathic pattern (Fig.…”

“…Among more than 40 examples (for review, see Ref. 34) hydropathic complementarity has been successfully applied to produce biologically active synthetic analogs of receptor binding sites (33,35,36) and ligands (37) and to map binding epitopes of natural ligands with their receptors (38,39). Also, hydropathic complementarity has been shown to determine several peptide-antibody interactions (40).…”

Chlamydia pneumoniaeinfection enhances lectin-like oxidized low-density lipoprotein receptor (LOX-1) expression on human endothelial cells

“…In the present experimental system, however, the concentrations of TNF‐α in the culture supernatant were below the detection limit (1 pg mL −1 ) and the presence of anti‐TNF‐α antibody during infection did not reduce the LOX‐1 induction (data not shown). Furthermore, the addition of an angiotensin II receptor inhibitor peptide was also ineffective at 50 μM, which was far above the effective dose (Dillon et al , 1998) (Fig. 5).…”

Small Molecule Complementarity As A Source of Novel Pharmaceutical Agents and Combination Therapies

“…In at least two cases --an antisense peptide to angiotensin II [27] and antisense peptides to enkephalins [28] --the antisense peptide enhanced peptide activity in vitro. The mechanism by which such enhancement occurs has not been elucidated, but might provide fertile ground for investigation.…”