Increased sensitivity to neurotensin in fasted rats.
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Angiotensin II↗
Biomedical subjects
S St-Pierre
Publications and source records attributed to S St-Pierre.
Studies on the inhibitory action of somatostatin in the electrically stimulated rat vas deferens.
Somatostatin (SS) inhibits in a dose-dependent manner electrically evoked contractions in the rat vas deferens. This action was not modified by yohimbine, naloxone or a mixture of antagonists containing atropine, phentolamine, methysergide, burimamide, propranolol and indomethacin, but was markedly potentiated by reducing the Ca2+ concentration of the medium from 2.5 to 1.25 mM and greatly inhibited when increasing the Ca2+ concentration of the medium from 2.5 to 5.0 mM. Clonidine (CLO), but not beta-endorphin (ENDO) was affected similarly to SS by changing the Ca2+ concentration of the medium. The contractile effect of norepinephrine in unstimulated rat vas deferens was not altered by SS. These results were taken as an indication that SS produces its inhibitory action in the rat vas deferens by interacting with specific SS and its receptors presumably located in the cell membranes of adrenergic nerve terminals. The interaction between SS and its receptors may provoke a decreased diffusion of Ca2+ ions into the nerve terminals and/or a decreased mobilisation of Ca2+ ions from intraneuronal stores thus leading to a reduction in electrically evoked release of norepinephrine.
Animals↗
Neurotensin-induced coronary vessels constriction in perfused rat hearts.
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Animals↗
An analysis of the negative inotropic action of somatostatin.
1 Somatostatin (SS) was evaluated as a chronotropic and inotropic agent in isolated spontaneously beating auricles of rats, rabbits and guinea-pigs.2 SS was completely inactive in rat and rabbit auricles but exerted a dose-dependent, negative inotropic effect in guinea-pig auricles in concentrations between 1.5 x 10(-8) to 1.2 x 10(-6) M.3 The negative inotropic effect of SS (6.0 x 10(-8) and 3.0 x 10(-7) M) was not inhibited by a mixture of antagonists containing practolol (7.9 x 10(-6) M), phentolamine (3.5 x 10(-7) M), methysergide (2.8 x 10(-7) M), diphenhydramine (3.9 x 10(-5) M), cimetidine (4.0 x 10(-5) M) atropine (3.4 x 10(-7) M) and indomethacin (1.4 x 10(-5) M).4 The negative inotropic effect of SS was greatly potentiated by reduction in the Ca(2+) concentration of the medium from 5.0 to 1.25 mM.5 On a molar basis, SS was equipotent with acetylcholine (ACh) as a negative inotropic agent in the guinea-pig auricles.6 SS (6.0 x 10(-8) and 6.0 x 10(-7) M) was found to inhibit selectively the positive inotropic action of neurotensin (NT) in guinea-pig but not in rat auricles.7 The inhibitory action of SS against NT was independent of its negative inotropic action.8 These results suggest that SS produces its negative inotropic action by interacting with specific receptors presumably located in the cell membrane of guinea-pig atria. The interaction between SS and its receptor may cause a decreased Ca(2+) diffusion and/or transport into the atrial cells. The physiological and pharmacological significance of these results is discussed.
Acetylcholine↗
Synthesis of peptides by the solid-phase method. IV. Des-Arg(9)-bradykinin and analogs.
We have synthesized a series of 19 analogs of the octapeptide fragment of bradykinin (BK), des-Arg 9-bradykinin, in order to perform a structure-activity study of this peptide on the newly discovered B1 receptor of bradykinin. The first time, each residue of the octapeptide was replaced by L-alanine to pinpoint biologically important residues. Thereafter, both phenylalanine residues in positions 5 and 8 were substituted by L-tyrosine methyl ether, L-cyclohexylalanine, D-phenylalanine, and L-leucine. This paper describes the synthesis of the analogs by the solid phase method. A Beckman peptide synthesizer was used to assemble the peptides on the resin support. Couplings were performed by the symmetrical anhydribe procedure. After cleavage with liquid HF, the peptides were purified by ion-exchange chromatography on carboxymethyl-cellulose and by gel filtration on Bio-Gel P2 resin. The purity of the octapeptides was then checked by tic, paper electrophoresis, amino acid analysis, and elemental analysis. The new peptides were tested on the rabbit aorta in order to evaluate their kinin-like activities and to see if they act as antagonist. The results of the biological assays are discussed in terms of structure-activity relationships.
Amino Acids↗
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↗
Liquid-phase method for peptide synthesis utilizing photolytic cleavage from a new o-nitrobenzoyl polyethylene glycol support.
Photolysis as a method for removal of a tert-butyloxycarbonyl-protected peptide possessing a free C-terminal carboxyl group from a polystyrene support in the solid-phase method of peptide synthesis was introduced by Rich, D. H. and Gurwara, S. K.((1975) J. Am. Chem. Soc. 97, 1575-1578). Using this basic concept we prepared a photosensitive 3-nitro-4-bromomethylbenzoyl polyethylene glycol support for use in the liquid-phase method of peptide synthesis. Photolytic cleavage of a protected tetrapeptide possessing a free C-terminal carboxyl group from the polyethylene glycol support resulted in a 98% yield compared with a 69% yield for the photolytic leavage from the polystyrene support. This application of photolysis as a cleavage method in liquid-phase peptide synthesis avoids the low yields and rather drastic conditons needed to remove a peptide attached directly to the poly-ethylene glycol support in the conventional liquid-phase method.
Alanine↗
Synthesis and conformation of sequential polypeptides containing epsilon-benzyloxycarbonyl-lysine and benzyl esters of aspartic and glutamic acids.
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Amino Acid Sequence↗
Squamous cell carcinoma of the maxillary sinus: analysis of 66 cases.
A retrospective review was performed of 66 patients with squamous cell carcinoma of the maxillary sinus. The majority of patients presented with tumors classified as T3 (31.8%) and T4 (54.5%). Seven (10.6%) patients presented initially with neck metastases and 13 (19.7%) patients subsequently developed regional disease. For the 66 patients studied, the observed 5 and 10 year actuarial survival rate was 27.3% and 20.7% respectively. The presence of cervical metastases, particularly when they developed subsequent to initial therapy, was associated with a poorer survival rate. Five year survival rate for patients without cervical metastases was 32.6% in contrast to 28.6% for patients initially presenting with nodal disease and 7.7% for patients who subsequently developed regional metastases. Overall, 5-year survival rate for all patients with cervical metastases was 15.0%. A combined treatment regimen (surgery and radiation therapy) appeared to be superior to single modality therapy. A 58.0% observed 5-year actuarial survival rate was achieved with combined therapy. Surgery or radiation therapy when used alone as a single modality resulted in a 5-year survival rate of 20.0% and 15.7% respectively.
Actuarial Analysis↗
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↗
Bronchoconstrictor action of neuropeptide Y (NPY) in isolated guinea pig airways.
Responses of various preparations of guinea pig and rat airways to synthetic porcine neuropeptide Y were analysed in vitro. NPY in doses up to 10(-6) M, induced a dose dependent contraction in trachea, bronchi and lung parenchymal strips of the guinea pig but did not have any effect in similar preparations obtained from the rat. In guinea pig airways the contractile responses to NPY were small in size and characterized by a slow onset and a long duration. This effect of the peptide was not dependent on pre-junctional nerve stimulation but rather mediated through the secondary generation of cyclooxygenase products. It is concluded that NPY may contribute per se to regulating the resting tone of guinea pig airways.
Animals↗
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↗
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↗
400 MHz NMR study on the C-terminal fragment 21-28 of vasoactive intestinal peptide.
A conformational study of the C-terminal fragment 21-28 of vasoactive intestinal peptide (VIP) was carried out by high resolution NMR spectroscopy. All spectral data were recorded with a Brüker 400 MHz spectrometer. The correct assignment of peaks was determined by specific homonuclear decoupling and by titration. The chemical shifts of amide protons were measured as a function of temperature in order to detect the presence of intramolecular hydrogen bonds. A tridimensional structure is proposed for the peptide.
Gastrointestinal Hormones↗
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↗
Histamine release by neurotensin in the rat hindquarter: structure-activity studies.
Histamine releasing effects of neurotensin (NT) and several NT fragments and structural analogues were measured in the rat perfused hindquarter. The results show that the chemical groups responsible for histamine release are located in the C-terminal sequence Arg9-Pro10-Tyr11-Ile12-Leu13-OH. Both the spatial configuration and positive charge of Arg8 and Arg9 appear to contribute to the histamine releasing effect of NT. Optimization of the histamine releasing effect of NT requires both a free C-terminal carboxyl group and the presence in position 11 of NT of an aromatic residue, with the L-configuration, bearing an heteroatom capable of hydrogen bonding with the receptor. The results indicate that the structural requirements of NT to induce histamine release from the rat perfused hindquarter are similar to those involved in other peripheral biological actions of NT.
Animals↗
Synthesis, conformational studies and biological activities of VIP and related fragments.
VIP and related fragments were prepared by the solid-phase method. The peptides were assembled on a benzhydrylamine resin and couplings of the Boc-amino acids were carried out by the symmetrical anhydride method. Cleavage was achieved by treatment with liquid HF and purification was accomplished by successive steps of cation exchange, partition and semi-preparative high pressure liquid chromatography. The biological activities were evaluated in vitro in the rabbit perfused heart and in vivo on the rat blood pressure. Structural studies were performed by high resolution (400 MHz) 1H-NMR spectroscopy and circular dichroism. The results show that among all the fragments tested, only VIP2-28 retains significant biological activity. The fragments 1-14 and 15-28, which are devoid of activity, were found to be inactive as antagonists. VIP and some of the fragments tend to adopt the helical structure, as demonstrated by spectroscopic techniques.
Amino Acid Sequence↗
Characterization of the histamine releasing effect of neurotensin in the rat heart.
Bolus injections of neurotensin (NT) in the rat perfused heart elicited a transient, dose-dependent histamine release. The histamine releasing effect of NT appears to be independent of the heart rate and coronary perfusion pressure and it was not influenced by atropine, propanolol, prazosin, methysergide, ketanserin, indomethacin, morphine, lidocaine or by removal of the atria. However, it was potentiated by adenosine, inhibited by sub-stimulatory concentrations of NT and the mast cell membrane stabilizing drug cromoglycate but was unaltered by the calcium antagonist verapamil. The absence of calcium in the heart perfusate suppressed the histamine releasing effect of NT. These results suggest that the histamine releasing effect of NT in the rat heart results from a direct effect on ventricular mast cells and is calcium-dependent.
Adenosine↗