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Biomedical subjects

R Couture

Publications and source records attributed to R Couture.

At least 109 records · Page 6Linked to original sources
PubMed1985

Choline acetyltransferase activity in the rat trigeminal system.

Choline acetyltransferase activity was investigated in the superior cervical ganglia and in six microdissected regions of the medulla oblongata of the rat ipsilateral and contralateral to electrolytic lesions of the trigeminal sensory ganglia (Gasserian). Electrolytic lesions of the Gasserian ganglia failed to modify levels of enzymatic activity in all structures studied. This result would be an argument against the existence of a major cholinergic population of sensory neurones in the trigeminal system.

Animals↗
PubMed1985

Trigeminal antidromic vasodilatation and plasma extravasation in the rat: effects of acetylcholine antagonists and cholinesterase inhibitors.

Antidromic stimulation of sensory peripheral branches of the trigeminal system (mental nerve) leads to cutaneous vasodilatation and increases vascular permeability in the rat. Antidromic vasodilatation is observed only at high intensity stimulation (10 V, 15 Hz, 0.2 or 5 ms) supporting the participation of afferent C-fibres in cutaneous dilator responses. Both antidromic vasodilatation and neurogenic plasma extravasation are significantly reduced by muscarinic antagonists suggesting that a cholinergic component may be involved in these trigeminal neurogenic responses. Neurogenic plasma extravasation remains unchanged by hexamethonium while antidromic vasodilatation is reduced. This latter effect may be merely a consequence of the dramatic fall in arterial pressure produced by the ganglion blocker. Antidromic vasodilatation is increased or unaffected by acetylcholinesterase inhibitors. On the other hand, the reduction of the plasma extravasation observed with these drugs could be due to their known ability to decrease the amount of acetylcholine released.

Acetylcholine↗
PubMed1984

Studies on the trigeminal antidromic vasodilatation and plasma extravasation in the rat.

Antidromic stimulation of sensory peripheral branches of the trigeminal system (mental nerve) led to cutaneous vasodilatation and increased vascular permeability in rats anaesthetized with urethane. The antidromic vasodilatation observed in intact animals was not altered by decentralization or sympathectomy. Both antidromic vasodilatation and neurogenic plasma extravasation remained unaffected by pre-treatment with cimetidine, indomethacin, baclofen, guanethidine plus phentolamine and propranolol, but were significantly reduced by cimetidine plus mepyramine and atropine, suggesting that cholinergic and histaminergic components might be involved in the sensory neurogenic responses. Methysergide reduced only the extravasation, suggesting that probably serotonin liberated by mast cells upon sensory stimulation can contribute to the neurogenic responses. In tests using substance P (SP) antagonists (D-pro4, D- trp 7, 9, 10)-SP (4-11) and (D-pro2, D-trp 7, 9)-SP it was found that they are more active in reducing the neurogenic extravasation than the vasodilatation. In addition it was observed that (D-pro 4, D-trp 7, 9, 10)-SP (4-11) was the most potent substance P antagonist in reducing the plasma extravasation and antidromic vasodilatation resulting from sensory stimulation.

Animals↗
PubMed1984

Characterization and immunocytochemical application of monoclonal antibodies against enkephalins.

Monoclonal antibodies were produced following immunization of mice with either [Leu5]enkephalin-bovine serum albumin or [Met5]enkephalin-keyhold limpet hemocyanin conjugates. Two monoclonal antibodies coded NOC1 and NOC2, respectively, were derived. These monoclonal antibodies did not discriminate between Leu- and Met-enkephalin in either radioimmunoassay or immunocytochemistry. NOC1 was characterized in detail. In radioimmunoassay NOC1 displayed about 40% crossreactivity with C-terminal extended Met-enkephalin hexapeptides and 7% with the extended heptapeptide (-Arg-Phe-OH), but did not recognize other endogenous peptides. In immunocytochemistry the NOC1 and NOC2 recognized all well-established "enkephalin immunoreactive sites," but they did not bind to areas known to contain beta-endorphin or high levels of pro-enkephalin. NOC1 was shown to be a suitable tool to demonstrate enkephalin immunoreactive sites by radioimmunocytochemistry utilizing both internally and externally labeled monoclonal antibodies.

Amino Acid Sequence↗
PubMed1982

Synthesis of peptides by the solid-phase method. 7. Substance P and analogues.

Substance P and 21 related peptides containing isosteric or isofunctional groups were prepared by the solid-phase method. After purification by gel filtration and ion-exchange chromatography, the compounds were characterized by thin-layer chromatography, paper electrophoresis, and amino acid and elemental analysis. The biological activities of the peptides were evaluated in vitro on the guinea pig ileum, the rabbit mesenteric vein, and the dog common carotid artery and in vivo on the rat blood pressure. It is shown that the replacement of some residues in the undecapeptide substance P causes variable losses of apparent affinity with a little or no change in the intrinsic activity. All the analogues used in the present study were found to be inactive as antagonists.

Animals↗
PubMed1982

Synthesis and biological activities of photoaffinity labeling analogues of substance P.

Substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-MetNH2, SP) is an undecapeptide with important properties as a neurotransmitter and with other functions. No specific antagonists and no long-acting analogues of this peptide hormone are known to date. In order to reach these goals, analogues of SP have been prepared which contain potential affinity, as well as photoaffinity labeling functions, suitable for irreversible attachment to SP receptors. We report here the synthesis of SP analogues which have the Phe residues in positions 7 or 8 replaced with (4'-NO2)Phe, (4'-NH2)Phe, (4'-N2+)Phe, and (4'-N3)Phe. Some of these peptides are used for photoaffinity labeling studies using various bioassays. The synthesis of the (NO2)Phe-containing peptide was carried out on solid phase using Nle instead of Met and the Boc strategy up to residue 4; the remaining amino acids were added using an Fmoc strategy. The protected undecapetide was cleaved by ammonolysis, purified by chromatography on silica gel with chloroform/methanol and deprotected afterwards. The amino, diazonium, and azido peptides were obtained in this sequence by chemical modification of the nitro peptides. On guinea pig ileum the modified peptides in position 8 had close to maximal activity, whereas modifications in position 7 produced some reduced activity, especially the nitro modification. No diazonium peptide produced any irreversible effects on guinea pig ileum. Photoinactivation studies were carried out on strips of guniea pig trachea, but no irreversible effects have been observed, neither permanent stimulation nor permanent inactivation. The biological activities and effects are discussed in view of the molecular properties of the synthesized analogues.

Affinity Labels↗
PubMed1982

Structure-activity studies on the C-terminal amide of substance P.

Twelve C-terminal heptapeptide analogues of substance P have been synthesized by solid phase and by the classical solution method. The modifications concerned all the C-terminal primary amide of SP and should therefore help to understand the biological significance of this carboxamide, as evaluated by in vivo and in vitro bioassays. From the results it can be seen that not the slightest change of the two amide protons is tolerated without an important loss of activity: replacement of one or two amide protons with alkyl groups, extension of the amide to the hydrazide and its alkyl analogues, and exchange of the amide with an ester or a carboxylic acid all reduce the relative activity/affinity at least by 2-fold. It is not clear for what reason all these modifications produce such a drastic activity reduction.

Animals↗
PubMed1982

Pharmacological effects of peptides on tracheal smooth muscle.

Peptide and non-peptide agents were tested for their stimulatory or inhibitory effects on circular strips of guinea pig isolated tracheae. Substance P, eledoisin, physalaemin, neurotensin, angiotensin, histamine and carbachol were found to contract, while noradrenaline, dopamine, bradykinin, nucleotides (AMP, ADP, ATP) and prostaglandins (PGE1, PGE2, PGA2) induced concentration-dependent relaxations of tracheae contracted with substance P or carbachol. Indomethacin (2.8 X 10(-6) M) significantly potentiated the effect of substance P and blocked that of bradykinin. The contractions to substance P of tissues treated with indomethacin were not modified by atropine, methysergide, diphenhydramine, cimetidine, propranolol, phentolamine, [Leu8]-ATII, [Leu8]-des-Arg9-bradykinin, naloxone and baclofen. The order of potency of C-terminal fragments of substance P was: hexa(6-11) greater than hepta(5-11) greater than substance P greater than = octa(4-11). It is concluded that the guinea pig isolated trachea is a pharmacological preparation sensitive to numerous agents and useful for studying structure-activity relationship and the mechanism of cellular action of several peptides, particularly substance P.

Animals↗
PubMed1981

Inactivation of substance P and its C-terminal fragments in rat plasma and its inhibition by Captopril.

The metabolic degradation of substance P(SP), some of its C-terminal fragments, and some analogues by rat plasma has been evaluated from the disappearance of the biological activities of these peptides on the guinea pig isolated ileum. The experiments were performed by dissolving each peptide in saline and by adding 20% (v/v) of rat plasma for incubation at 37 degrees C for various periods of time. It was found that SP and octapeptide 4-11 are inactivated quite rapidly and at approximately the same rate whereas SP-free acid, heptapeptide 5-11, hexapeptide 6-11, and [D-Trp8]-SP are inactivated more slowly. The replacement of Phe7 by D-Trp does not protect the undecapeptide SP from inactivation. The degradation of SP and of all the C-terminal fragments was completely blocked by Captopril at a concentration of 10 micrograms/mL of plasma. Under these conditions, Captopril also slightly reduced the rate of inactivation of bradykinin and of SP-free acid. These results were interpreted as indicative of the presence in rat plasma of an endopeptidase that hydrolyses a peptide bond in the C-terminal pentapeptide sequence of SP. This endopeptidase is completely inactivated by Captopril, which thus appears to be not as specific for the angiotensin-converting enzyme as it was thought to be.

Animals↗
PubMed1980

Synthesis of peptides by the solid-phase method. V. Substance P and analogs.

We have synthesized a series of 12 analogs of the undecapeptide substance P in order to perform a structure-activity study of this peptide. In the present work, each residue was substituted by L-alanine, and the C-terminal amide was replaced by the free carboxyl in order to pinpoint biologically important side chains and functional groups. The synthesis of the analogs was carried out by the automatic solid-phase method. Couplings were performed by the symmetrical anhydride procedure. After cleavage with liquid HF, the peptides were purified by gel filtration and ion-exchange chromatography. Their purity was assessed by thin-layer chromatography, paper electrophoresis, amino acid and elemental analyses, and high pressure liquid chromatography. They were tested for biological activity in vitro on the ileum of the guinea pig, the mesenteric vein of the rabbit, and the vas deferens of the rat, and in vivo by measuring their effect on the blood pressure of the rat.

Animals↗
PubMed1980

The dog common carotid artery: a sensitive bioassay for studying vasodilator effects of substance P and of kinins.

In order to develop a sensitive pharmacological preparation which would allow the measurement of the inhibitory effects of kinins and substance P (SP) in vascular smooth muscles, several large arteries of the dog were studied in vitro. The common carotid artery was found to be one of the most sensitive preparations to SP and kinins. When contracted with low concentrations of noradrenaline (between 3.0 x 10(-8) and 3.0 x 10(-7) M), this artery responds to SP (6.5 x 10(-11)-6.5 x 10(-9) M) and bradykinin (BK) (8.1 x 10(-11)-9.1 x 10(-8) M) with relaxations that are proportional to the concentrations of the two peptides. SP and BK appear to exert their relaxant effects through the activation of specific receptors as the exposure of the common carotid artery to concentrations of [Leu8]-angiotensin II, propranolol, methysergide, cimetidine, or atropine sufficient to inhibit the effects of the corresponding agonists do not affect the relaxing effect of SP and BK. [Leu8]-des-Arg9-BK (1.0 x 10(-6) M), indomethacin (2.8 x 10(-5) M), and lioresal (4.7 x 10(-5) M) are also inactive. When the dog common carotid artery is desensitized with high concentrations of SP, BK, eledoisin, and physalaemin a cross-desensitization is observed only between SP and physalaemin. These results support the conclusion that SP and kinins act on different receptors. The order of potency of kinins is the following: BK = [Tyr(Me)8]-BK greater than des-Arg9-BK, suggesting that the receptor for kinins is of the B2 type. The order of potency of peptides related to SP is SP greater than C-terminal 4-11 greater than C-terminal hexapeptide 6-11, similar to that observed in other vascular preparations. The results summarized in this paper indicate that the dog common carotid artery is a preparation sensitive to SP and BK and useful for studying the relaxant effect of these two peptides on vascular smooth muscles.

Animals↗
PubMed1980

Vascular reactivity to angiotensin and noradrenaline in rats. Effect of aging and of uninephrectomy.

The effects of angiotensin II (ATII), and noradrenaline (NA) were measured in vivo and in several vascular preparations taken from normotensive intact or from uninephrectomized rats receiving NaCl 0.9% for drinking. The study was directed to evaluate the effects of aging and of uninephrectomy plus NaCl administration on vascular reactivity. Aging neither change the response in vivo or the myotropic effects of the agents in the isolated portal vein, while the effect of ATII was specifically increased in the perfused kidney, and both the response to ATII and NA were decreased in rat hindquarters and thoracic aortae. Uninephrectomy and NaCl administration were accompanied by a selective increase of sensitivity to ATII in vivo and in the isolated kidney, by a stronger effect of both ATII and NA in the hindquarter, while the response of the portal vein did not change and those of the thoracic aorta to ATII and NA showed a tendency to diminish. These results indicate that aging and uninephrectomy have to be taken into account in studies intended to evaluate the sensitivity of vascular preparations of normotensive and hypertensive rats.

Aging↗
PubMed1980

Vascular reactivity to angiotensin and noradrenaline in rats maintained on a sodium free diet or made hypertensive with desoxycorticosterone acetate and salt (DOCA/salt).

The pressor response to angiotensin II (ATII) and to noradrenaline (NA), as well as the response of vascular beds (hindquarter and kidney) isolated and perfused with Krebs' solution, and the contractions of strips of thoracic aortae, portal veins to the same agents were measured in animals and organs taken from rats maintained on a sodium free diet or made hypertensive with DOCA/salt and in several groups of controls. The myoptropic effects of ATII and of 5HT were compared in stomach fundi. The main purpose of the study was to find out how a reduction or an increase of total body sodium and the associated changes of renin production can influence the vascular response to angiotensin and to catecholamines. Reduction of sodium in the diet was accompanied by no changes or a decrease of the responses of isolated vascular beds and tissues to ATII and NA; the pressor effect of ATII was also reduced, while that of NA was definitely increased. Treatment with DOCA/salt and the resulting hypertension were accompanied by an increased vascular response to ATII in vivo, to ATII and NA in the isolated hindquarter, while the other preparations (the perfused kidney, the thoracic aorta and the stomach fundus) showed a decreased response specific for ATII (in the kidney and the aorta) and to both ATII and 5HT (in the stomach). The responses of the portal vein to ATII and NA were unchanged. These results are discussed in relation to the changes of renin production, occuring in the two experimental conditions, and with respect to the various mechanisms currently considered for explaining the changes of vascular reactivity in hypertension.

Angiotensin II↗
PubMed1980

Vascular reactivity to angiotensin and noradrenaline in spontaneously and renal hypertensive rats.

Vascular reactivity to angiotensin II (ATII) and noradrenaline (NA) have been studied in vivo and in femoral and renal vascular beds taken from spontaneously hypertensive rats (S.H.R.) of 3 and 5 months of age. Moreover, the stimulating effects of the same agents have been measured in strips of thoracic aortae, portal veins and stomach fundi taken from S.G.R. and from renal hypertensive rats (R.H.R.) three weeks after clamping one renal artery (two kidneys hypertention). Results obtained in animals or in organs derived from the two groups of hypertensive rats were compared with controls of the same age or of the same weight. It was found that the pressor response to ATII is increased in S.H.R. while that of NA remains unchanged. The myotropic effects of ATII and NA are definitely increased in hindquarters, kidneys and strips of veins of S.H.R., while the responses of thoracic aortae and of stomach fundi are depressed. No changes are observed in the responses of aortae, veins or stomachs of R.H.R. compared to controls. These results are discussed and compared to those obtained in DOCA/salt hypertensive animals (8) in an attempt to explain the mechanisms underlying the increased pressor effect of angiotensin in rats affected by three forms of experimental hypertension.

Aging↗