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Biomedical subjects

P Gaudreau

Publications and source records attributed to P Gaudreau.

102 records · Page 6Linked to original sources
PubMed1979

Structure-activity studies of [des-Arg9]-bradykinin on the B1 receptor of the rabbit aorta.

Eight L-alanine analogues of [des-Arg9]-bradykinin and a few other compounds substituted in positions 5 and (or) 8 have been tested on rabbit aortic strips in order to identify the group(s) responsible for binding and (or) stimulation of the B1 receptor. The results obtained with the L-Ala series have shown that the active group is located at the C-terminal end and it is probably Phe8, while the middle part and the N-terminal end of the peptide molecule are primarily involved in binding the agonist to the receptor. An aromatic ring is required in position 8 for activation of receptors, since the elimination or aromaticity (as in [Leu8,des-Arg9]-bradykinin and in [cyclohexylalanine8,des-Arg9]-bradykinin) brings about pure and competitive antagonists. Some compounds exert an angiotensin-like effect when applied at very high concentrations.

Alanine↗
PubMed1979

Biological activities of kinins modified at the N- or at the C-terminal end.

A series of analogues of des-Arg9-bradykinin, modified at the N- or C-terminal end, were tested on rabbit aorta strips (receptor B1) and on cat ileum strips (receptor B2) in an attempt to find long-acting agonists and antagonists. It was found that the methylation or the amidation of the C-terminal carboxyl reduces the affinity and (only the amidation) the intrinsic activity of the agonists, while not changing significantly the duration of action of both agonists and antagonists. The addition of a Lys at the N terminal is accompanied by a marked increase of affinity, no changes of intrinsic activity, and a prolongation of the duration of action of agonists. Antagonists behave in a similar way as the agonists and show increased affinity; the time required for inducing full inhibition as well as the duration of action are significantly increased. The pharmacological and physiopathological implications of these results are discussed.

Amides↗
PubMed1977

Comparative studies on EBV antigens by immunofluorescence and immunoperoxidase techniques.

Three groups of EBV antigens, VCA, MA and EA, were compared by the techniques of electron microscopic immunoperoxidase (IP) and immunofluorescence (IF). P3HR-1 and EBV superinfected Raji cells served as targets for labelled sera from patients with BL, NPC and IM or from healthy donors. 125I peroxidase-labelled antibodies were also prepared to determine, autoradiographically, the penetration of the complex into the cell system, and to monitor the incubation and washing procedures. The development of a gentle sedimentation technique proved critical in handling the fragile target cells. VCA and MA were readily identified and localized by both procedures without significant modification of the basic techniques. Indentification of early antigens by IP required modification of the fixation method to include a brief treatment in acetone. The diffuse early antigen (EAD) was found to be associated with cellular ribosomes.

Antigens, Viral↗
PubMedDate not supplied

Localization of cholecystokinin receptors in relation to the nigrostriatal and mesolimbic dopaminergic pathways.

The anatomical distribution of cholecystokinin (CCK)-dopamine (DA) neurons suggests that CCK could modulate dopaminergic activity. To further investigate that hypothesis, the cellular localization of CCK receptors was ascertained in relation to mesolimbic and nigrostriatal DA pathways after a series of chemical lesions induced with ibotenic acid and 6-hydroxydopamine. The results suggest that CCK receptors are not localized on dopaminergic neurons of the nigrostriatal and mesolimbic pathways.

Animals↗
PubMedDate not supplied

Autoradiographic distribution of [3H]neurotensin receptors in rat brain: visualization by tritium-sensitive film.

[3H]Neurotensin ([3H]NT) binds specifically to a single class of binding sites on slides-mounted sections of rat brain 1Kp = 5.1 nM; Bmax = 16.2 fmol/mg tissue). Bound [3H]NT can be displaced by nonradioactive NT and a series of its fragments and analogues with relative potencies that correlate closely (r = 0.89; p less than 0.01) to their potencies in the rat stomach strip bioassay. These results suggest that NT receptors are similar in both systems. [3H]NT binding sites were visualized by using tritium-sensitive LKB film analysed by computerized densitometry. [3H]NT receptors are highly concentrated in the external layer of the olfactory bulb, in the rhinal sulcus, in certain nuclei of the amygdala, in the substantia nigra, zona compacta and in the ventral tegmental area. The high density of [3H]NT receptors in the last two areas suggest an interaction between NT and brain dopaminergic systems such as the nigrostriatal and the mesolimbic pathways.

Animals↗
PubMedDate not supplied

Localization of neurotensin binding sites in rat kidney.

[3H]Neurotensin ([3H]NT) appears to bind specifically to a single class of sites in slide-mounted rat kidney sections (KD = 8.3 nM; Bmax = 31.6 fmol/mg tissue). Bound [3H]NT can be displaced by nonradioactive NT and a series of its fragments and analogues with relative potencies that correlate well (r = 0.91; p less than 0.005) to their potencies in the rat stomach strip bioassay. These results suggest that NT receptors are similar in both systems. However, they are probably slightly different from those present in the guinea pig atria (r = 0.78; p less than 0.1). We visualized these sites by using the tritium-sensitive LKB film technique analysed by computerized densitometry. [3H]NT binding sites are highly concentrated in the renal cortex while low levels are observed in the renal medulla. The possible physiological and/or pathophysiological significances of the presence of [3H]NT binding sites in the kidney are discussed.

Animals↗
PubMedDate not supplied

Characterization and visualization of cholecystokinin receptors in rat brain using [3H]pentagastrin.

[3H]Pentagastrin binds specifically to an apparent single class of CCK receptors on slide-mounted sections of rat brain (KD = 5.6 nM; Bmax = 36.6 fmol/mg protein). This specific binding is temperature-dependent and regulated by ions and nucleotides. The relative potencies of C-terminal fragments of CCK-8(SO3H), benzotript and proglumide in inhibiting specific [3H]pentagastrin binding to CCK brain receptors reinforce the concept of different brain and pancreas CCK receptors. CCK receptors were visualized by using tritium-sensitive LKB film analyzed by computerized densitometry. CCK receptors are highly concentrated in the cortex, dentate gyrus, granular and external plexiform layers of the olfactory bulb, anterior olfactory nuclei, olfactory tubercle, claustrum, accumbens nucleus, some nuclei of the amygdala, thalamus and hypothalamus.

Animals↗
PubMedDate not supplied

Catabolism of rat growth hormone-releasing factor(1-29) amide in rat serum and liver.

Clinical and veterinary uses of growth hormone-releasing factor [GRF(1- 29)NH2] require the design of analogs that are resistant to proteolysis by serum and liver degrading enzymes. This study investigated rat GRF(1-29)NH2 processing in serum and liver homogenate by means of high pressure liquid chromatography (HPLC). Synthetic rGRF(1-29)NH2 (30 microM) was incubated (0-120 min, 37 degrees C) in serum (49 +/- 8 mg prot./ml). The rGRF(1-29)NH2 (10 microM) was also incubated (0-120 min, 37 degrees C) with liver homogenate (200 +/- 6 micrograms prot./ml). Time course studies of rGRF(1-29)NH2 disappearance showed apparent half-lives of 18 +/- 4 min and 13 +/- 3 min in serum and liver homogenate, respectively. This was accompanied by the appearance of degradation products that were all less hydrophobic than the native peptide. In the serum, two major metabolites were detected and isolated by preparative HPLC. Combined results of amino acid analysis, sequencing, and chromatography with synthetic homologs revealed the presence of rGRF(1-20)OH and (3-20)OH. A small amount of rGRF(12-29)NH2, coeluting with rGRF(3-20)OH, was also found by sequencing. In the liver, rGRF(1-18)OH, (3-18)OH, and (1-10)OH were identified. The peptide bond Ala2-Asp3 (DPP IV cleavage site) was hydrolyzed in both serum and liver. Other tissue-specific cleavage sites were Arg11-Arg12 and Arg20-Lys21 (trypsin-like cleavage site) in the serum, and Tyr10-Arg11 and Tyr18-Ala19 (chymotrypsin-like cleavage site) in the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMedDate not supplied

Specific inhibition of herpesvirus ribonucleotide reductase by a nonapeptide derived from the carboxy terminus of subunit 2.

Ribonucleotide reductase, an essential enzyme for the synthesis of deoxyribonucleotides, is formed by the association of two nonidentical subunits in almost all prokaryotic and eukaryotic cells. The same model probably holds for the herpes simplex virus (HSV)-encoded ribonucleotide reductase; two polypeptides of relative molecular mass 136,000 (136K; H1) and 40K (H2) (referred to elsewhere as RR1 and RR2; see for example, Dutia et al.) have been associated with the viral enzyme by both genetic and immunological studies. Furthermore, DNA sequence analyses have shown significant stretches of amino-acid homology between these viral polypeptides and those of, respectively, subunit 1 (ref. 12) and subunit 2 (ref. 13) of the Escherichia coli and mammalian enzymes. To assess the involvement of the 40K polypeptide in reductase activity, we synthesized a nonapeptide corresponding to the sequence of its carboxy terminus with the intention of raising neutralizing antibodies specific for the viral activity (E.A.C. et al., in preparation). We report here the unexpected finding that the nonapeptide itself specifically inhibits the HSV ribonucleotide reductase activity in a reversible, non-competitive manner, and we suggest that it does this by impairment of the correct association of the two subunits. This phenomenon emphasizes the potential usefulness of synthetic peptides in probing critical sites involved in macromolecular interactions.

Amino Acid Sequence↗