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S St-Pierre

Publications and source records attributed to S St-Pierre.

At least 91 records · Page 5Linked to original sources
PubMed1992

N-terminal portion of motilin determines its biological activity.

This study aimed to identify the portion of the 22 amino acid sequence of motilin responsible for the biological activity of the peptide. The contraction of rabbit duodenal muscle in vitro was measured when exposed to synthetic fragments of motilin corresponding to various sequences of the C- or N-terminal portions of the molecule. Fragments 2-22 or 3-22 (where the initial amino acids of the N-terminal ending were removed) were more than 1000 times less potent than the native molecule 1-22. Fragment 1-9 (where the last 13 amino acids located at the C-terminal side of motilin were removed) was devoid of any contractile capacity, while synthetic fragments whose C-terminal structure extended beyond the 1-9 motilin sequence maintained almost complete biological activity. N-terminal amino acid sequence 1-9 is therefore an essential determinant of the contractile activity of motilin.

Animals↗
PubMed1991

Antiparkinson-like effects of neurotensin in 6-hydroxydopamine lesioned rats.

The aim of the present study was to examine the effects of neurotensin in an animal model of Parkinson's disease (PD). Bilateral administration of 6-OHDA in the medial forebrain bundle at the level of the posterolateral hypothalamus of rats resulted in the appearance of the 3 principal neurological signs of PD: hypokinesia, rigidity and tremor. These symptoms were accompanied by severe losses of dopamine and its main metabolites in terminal regions of well-known dopamine pathways. Norepinephrine concentrations were also decreased in several regions but to a lesser extent than dopamine. Intracerebroventricular administration of neurotensin, in doses ranging from 7.5 to 120.0 micrograms, resulted in dose related attenuations of both muscular rigidity and tremors of animals. However, hypokinesia, defined as decreased motor activity was not significantly affected by the peptide. Administration of 120.0 micrograms of [Ala]NT, an inactive analogue of neurotensin, failed to alter any of the 3 neurological signs. Together, these results reveal selective antiparkinson-like effects of neurotensin in an animal model. The theoretical significance of these findings is discussed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Structural determination of the vasoactive intestinal peptide by two-dimensional H-NMR spectroscopy.

The structure of the vasoactive intestinal peptide 1-28 in 40% 2,2,2-trifluoroethanol was investigated by two-dimensional 1H-nmr spectroscopy. All 1H resonances, except the gamma, delta, and epsilon protons of the lysine residues, could be sequentially assigned. Numerous intraresidual as well as short-range interresidual nuclear Overhauser effect spectroscopy connectivities were observed. Using a variable-target function minimization, a molecular model consisting of two helical stretches involving residues 7-15 and 19-27 connected by a region of undefined structure was calculated. The existence of an undefined structure between residues 16 and 18 confers mobility to the peptide molecule.

Amino Acid Sequence↗
PubMed1991

Structure-activity studies of neurotensin on muscular rigidity and tremors induced by 6-hydroxydopamine lesions in the posterolateral hypothalamus of the rat.

It has previously been reported that intracerebroventricular administration of neurotensin (30 micrograms) reduced muscular rigidity and tremors, induced by a neurochemical lesion with 6-hydroxydopamine in the posterolateral hypothalamus of rats. In the present study, the effects of two fragments (NT1-10 and NT8-13) and two analogues ([D-Tyr11]-NT and [Ala11]-NT) of neurotensin on the grasping time (index of muscle rigidity) and tremors in 6-hydroxydopamine-lesioned rats are reported. Intracerebroventricular administration with 120 micrograms of NT1-10 and [Ala11]-NT had no effect on the muscle rigidity and tremors induced by the neurochemical lesion. The administration of NT8-13 60 micrograms) significantly attenuated both behavioural responses. The analogue [D-Tyr11]-NT produced a much greater attenuation of the muscle rigidity and tremors. The dose of 1.8 micrograms of [D-Tyr11]-NT significantly reduced the grasping time, while the number of tremors was attenuated with the threshold dose of 0.9 micrograms. Together, these results suggest that the effects of neurotensin on muscle rigidity and tremors, induced by pretreatment with 6-hydroxydopamine injected into the posterolateral hypothalamus, were not caused by non-specific effects but largely depended on the carboxy terminal of the peptide. The tyrosine residue in position 11 of the molecule plays a critical role in the action of neurotensin, as shown with the high potency and duration of action of the analogue [D-Tyr11]-NT. As previously suggested, the greater effect with [D-Tyr11]-NT may be due to greater resistance of the analogue to enzymatic degradation because of the incorporation of the D-Tyr amino acid, in position 11 of neurotensin.

Animals↗
PubMed1991

Neurotensin selectively antagonizes apomorphine-induced stereotyped climbing.

In order to better characterize the neuroleptic properties of neurotensin, the dose-related effects of the peptide on stereotyped climbing, sniffing and licking induced by 0.6 mg/kg apomorphine were examined. The following doses of the peptide were injected intraventricularly 30 min prior to apomorphine administration: 0.9, 3.75, 30.0 and 60 micrograms. Results indicate that, whereas oro-facial stereotypies remained unaffected by the peptide, stereotyped climbing was significantly decreased with the two largest doses of neurotensin. These findings indicate that the profile of neurotensin's neurobehavioral effects is more akin to that of atypical than typical neuroleptics.

Animals↗
PubMed1991

Reduction of the in vitro hemolytic activity of soybean lecithin liposomes by treatment with a block copolymer.

The in vitro hemolytic activity of liposomes made of soybean L-alpha-lecithin towards diluted (0.0086 v/v) human erythrocytes was used to investigate the effect of surface coating on the interaction of liposomes with cells. The increase in apparent volume of the block copolymer of ethylene glycol and propylene glycol, Pluronic F-127, in the presence of liposomes supports the hypothesis of either adsorption or penetration of the copolymer at the surface of the liposomes. When the liposomes are pre-incubated with Pluronic F-127, their lytic activity towards fresh erythrocytes is significantly reduced while it remains unchanged towards erythrocytes aged in vitro. It is also found that aging the liposomes has little effect on their lytic activity while aging of the erythrocytes makes them more fragile towards the liposomes. The results are discussed in terms of steric hindrance.

Erythrocytes↗
PubMed1991

Neurobehavioral profile of neuropeptide Y.

In order to better delineate the profile of central actions of neuropeptide Y (NPY), the effects of intracerebroventricular administration of several doses (2.5-20 micrograms) of the peptide on spontaneous activity, muscular tone, body temperature, food intake, nociception and cataleptic manifestations were examined in rats. Results indicate that, starting at 5 micrograms. NPY significantly decreased motor activity of animals in a dose-related fashion. NPY also significantly lowered body temperature of animals. The hypothermic effect was obtained following injections of 10.0 and 20.0 micrograms of the peptide. Administration of the same two doses of NPY resulted in significant increases in food intake, muscular tone and induced a significant catalepsy in animals. On the other hand, nociceptive response times of animals in the hot plate test were not affected by any of the NPY doses tested. Together, these results indicate that the profile of NPY's neurobehavioral actions is more complex than previously reported and suggest that the peptide might be implicated functionally in a variety of neurophysiological processes.

Animals↗
PubMed1991

Presynaptic inhibition by neuropeptide Y in rat hippocampal slice in vitro is mediated by a Y2 receptor.

1. The action of analogues and C-terminal fragments of neuropeptide Y (NPY) was examined on excitatory synaptic transmission in area CA1 of the rat hippocampal slice in vitro, by use of intracellular and extracellular recordings, to determine by agonist profile the NPY receptor subtype mediating presynaptic inhibition. 2. Neither NPY, analogues nor fragments of NPY affected the passive or active properties of the post-synaptic CA1 pyramidal neurones, indicating their action is at a presynaptic site. 3. The full-sequence analogues, peptide YY (PYY) and human NPY (hNPY), were equipotent with NPY at the presynaptic receptor, while desamido hNPY was without activity. 4. NPY2-36 was equipotent with NPY. Fragments as short as NPY 13-36 were active, but gradually lost activity with decreasing length. NPY 16-36 had no effect on extracellular field potentials, but still significantly inhibited excitatory postsynaptic potential amplitudes. Fragments shorter than NPY 16-36 had no measurable effect on synaptic transmission. 5. The presynaptic NPY receptor in hippocampal CA1 therefore shares an identical agonist profile with the presynaptic Y2 receptor at the peripheral sympathetic neuroeffector junction.

Action Potentials↗
PubMed1991

Comparative affinities and antagonistic potencies of various human calcitonin gene-related peptide fragments on calcitonin gene-related peptide receptors in brain and periphery.

Recent data have suggested that N-truncated human calcitonin gene-related peptide (hCGRP) fragments such as hCGRP8-37 and hCGRP12-37 behave as competitive antagonists in certain bioassays. The present study was undertaken to determine which amino acid residues between positions 8 to 12 are directly involved in ensuring high affinity and antagonist properties at CGRP receptors. In brain, atrium and vas deferens membrane preparations, hCGRP8-37 and hCGRP9-37 demonstrated affinities similar to or much higher than that of the native peptide hCGRP alpha. Shorter fragments such as hCGRP 10-37 and hCGRP 11-37 possessed less than 20% of the affinity of hCGRP alpha in these various assays demonstrating the critical importance of the Thr residue in position 9 for maintenance of adequate receptor affinity. In the in vitro guinea pig left and right atria bioassays, both hCGRP8-37 and hCGRP9-37 behaved as potent and competitive antagonists (pA2:7.0-7.7) of positive chronotropic and inotropic effects induced by hCGRP alpha. hCGRP 10-37 and hCGRP 11-37 were at least 10 times less potent (pA2: 6.1-6.6). Interestingly, both hCGRP 8-37 and hCGRP9-37 were much less potent (pA2: 6.2-6.3) in blocking the effects of hCGRP alpha in the rat vas deferens whereas only slight inhibition was observed at 1.0 microM with hCGRP10-37 and no blocking activity was detected with hCGRP11-37 at a low micromolar concentration. These results are in accordance with binding data and demonstrate further the importance of residues in positions 9 (Thr) and 10 (His) to ensure potent antagonistic properties of N-truncated hCGRP fragments.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1990

Effects of neurotensin on regional brain concentrations of dopamine, serotonin and their main metabolites.

The effects of neurotensin, 7.5 or 30 micrograms, on concentrations of DA, DOPAC, (HVA), serotonin 5-HT and 5-HIAA were measured in 8 regions of the rat brain either 5 or 30 min following intracerebroventricular administration. Regions examined include the frontal cortex, striatum, nucleus accumbens, amygdala, septum, hypothalamus, ventral tegmentum and substantia nigra. Results indicate that both doses of neurotensin significantly elevated concentrations of dopamine in the striatum and amygdala 5 min following injection. The effects of the peptide on DOPAC and HVA were more pervasive and enduring, with significant increases in metabolite levels occurring in both mesolimbic and nigrostriatal terminal regions. In order to assess effects on turnover of dopamine, the ratios of each metabolic to dopamine concentrations were examined. Results indicate that, while the DOPAC/DA ratio was elevated in many regions, the HVA/DA ratio was increased in all regions examined. The effects of neurotensin on serotoninergic parameters were less pervasive and more variable, with both increases and decreases in 5-HT and 5-HIAA concentrations being observed. The effects of the peptide on 5-HIAA/5-HT were limited to the nucleus accumbens, where this ratio was increased, and the ventral tegmentum, where 5-HIAA/5-HT was decreased. These findings reveal that the effects of the neurotensin on dopaminergic transmission are more widespread than previously reported in that all major dopamine pathways are affected by the peptide. Also, the observed changes in the ratios of both DOPAC and HVA to DA suggest that neurotensin enhances the turnover of this transmitter.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Structural study of the N-terminal segment of neuropeptide tyrosine.

A series of analogues of neuropeptide tyrosine (NPY) was synthesized by solid-phase peptide synthesis using BOP as a coupling reagent for the complete synthesis. A structure-activity study of the N-terminal portion of the molecule was performed with the analogues obtained by the successive replacement of the first 10 amino acids by the residue L-alanine. NPY and its analogues [Ala1-10]hNPY were tested for their potency on rat vas deferens and for their affinity to central nervous system receptors on a rat brain membrane preparation. The results suggest that the hypothetical polyproline type II helix structure of the N-terminal segment is involved in both potency and affinity. Indeed, the substitution by L-Ala of proline residues in position 2, 5, or 8 showed important losses of activity and affinity. The more important losses were observed with the replacement of Pro-5 or Pro-8. A critical loss of potency of hNPY was also observed after the substitution of the Tyr-1 residue by L-Ala, thus confirming the important role played by this residue for the full expression of the biological activity of NPY.

Alanine↗
PubMed1990

Inhibitory action of calcitonin gene-related peptide (CGRP) in the mouse colon.

The effect and mechanism of action of calcitonin gene-related peptide (CGRP) have been investigated on the mouse distal colon. CGRP caused a concentration-dependent relaxation which was not blocked by classical pharmacological antagonists. The response pattern was characterized by a relatively rapid onset and long sustained duration. The results suggest that CGRP itself may contribute to regulating the muscular tone of the mouse colon.

Animals↗
PubMed1990

Comparative structural requirements of brain neuropeptide Y binding sites and vas deferens neuropeptide Y receptors.

A series of fragments and analogues of neuropeptide Y (NPY), both human (hNPY) and porcine (pNPY), were synthesized and tested for their affinities at brain NPY receptor binding sites and their potencies in inhibiting the electrically stimulated twitch response of rat vas deferens. Results with N- and C-terminal fragments suggest that amino acid residues in the N-terminal portion of the molecule are mostly important for recognition of brain and vas deferens NPY receptors, in addition to being relevant for the maintenance of adequate receptor affinity. On the other hand, C-terminal amino acid residues appear to be responsible for triggering receptor activation in the rat vas deferens preparation, because full intrinsic activity is maintained with fragments up to NPY18-36. C-terminal fragment NPY25-36 and N-terminal fragment NPY1-15 were devoid of affinity for [3H]NPY brain receptor sites and showed no activity in the rat vas deferens preparation. Similarly, N-terminal fragment hNPY1-24CONH2 showed no affinity toward [3H]NPY brain receptor sites and no inhibition of the twitch response in the rat vas deferens preparation at concentrations up to 1.0 microM. On the contrary, this fragment appears to selectively increase the amplitude of the twitch response to electrical stimulation at low micromolar concentrations, an effect opposite to that of NPY and all other NPY fragments and analogues studied here. The exact mechanism mediating this contractile action of hNPY1-24CONH2 remains to be established. Modifications of the tyrosine residue in position 20 led to the development of two analogues, [D-Tyr20]hNPY and [D-Trp20]hNPY, which show an apparent preference for the vas deferens NPY receptor. On the other hand, substitutions of the tyrosine residue in position 21 by a phenylalanine ([Phe21]hNPY) or a methylated tyrosine residue ([Tyr-O-Me21]hNPY) produced analogues demonstrating an apparent preference for the brain receptor site. This suggests that modifications of tyrosine residues at positions 20 and/or 21 may eventually lead to the development of NPY analogues distinguishing between the most abundant class of sites present in the brain and vas deferens, respectively.

Amino Acid Sequence↗
PubMed1990

Stimulation of duodenal muscle contraction by porcine or canine motilin in the dog in vivo.

Motilin is a 22 amino acid polypeptide stimulating intestinal muscle contraction. Structure analysis of motilin purified from hog and from dog intestinal mucosa reveals different amino acids in positions 7, 8, 12, 13, and 14. Previous in vitro experiments suggested this species-related structural heterogeneity could generate different bioactive characteristics for these two peptides. This study was designed to compare the stimulatory mechanism of canine and porcine motilins on dog duodenal motility in vivo, testing the hypothesis that canine motilin stimulates a receptor located on the intestinal muscle, while porcine motilin is acting on intrinsic nerves regulating intestinal muscle contraction. Synthetic porcine and canine motilins were administered through a catheter inserted in the caudal pancreatic duodenal artery to stimulate the contraction of a close irrigated duodenal segment. In acute experiments performed on anaesthetized animals, both peptides induced a similar motor stimulation that was inhibited by tetrodotoxin and atropine. In experiments in conscious animals, canine and porcine motilins were equally potent in inducing premature phase III of the migrating motor complex, and the action of both peptides was abolished by atropine or hexamethonium. This study reveals that the structural heterogeneity between porcine and canine motilin does not influence the bioactivity of both peptides in the dog in vivo and suggests that circulating endogenous motilin stimulates intestinal muscle contraction through intrinsic excitatory nerves.

Anesthesia↗
PubMed1989

Effect of brain natriuretic peptide on dehydration- or angiotensin II-induced water intake in rats.

The present study was performed to evaluate the effect of 3rdV injection on water intake of brain natriuretic peptide (BNP), which is structurally different from the atrial natriuretic peptide. BNP was recently isolated from porcine brain and appears to have a different precursor than the family of atrial natriuretic peptides. Central administration of BNP 3rdV decreased water intake. At a dose of 2.0 nmol/rat, BNP partially inhibited dehydration-induced water intake and completely blocked the stimulatory effect of 478 pmol/rat angiotensin II in rats.

Angiotensin II↗