Biomedical subjects

S Lemaire

Publications and source records attributed to S Lemaire.

At least 55 records · Page 3Linked to original sources

PubMed1995

Histogranin, a modified histone H4 fragment endowed with N-methyl-D-aspartate antagonist and immunostimulatory activities.

Histogranin is a naturally-occurring pentadecapeptide with a structure 80% homologous with that a fragment-(86-100) of histone H4. First isolated from bovine adrenal medulla, the peptide was also shown to be present in the pituitary, brain, adrenal glands, blood plasma, lungs and spleen. At the subcellular level, histogranin is concentrated in secretory vesicles and it is released from perfused bovine adrenal glands 15-35 min after stimulation with carbamylcholine as opposed to catecholamines and [Leu5]enkephalin which are released immediately after stimulation. Rat brain membranes possess specific binding sites for [125I][Ser1]histogranin with characteristics of a receptor, namely high affinity, saturability, reversibility and sensitivity to heat and proteolytic enzyme treatments. Intracerebroventricular injections of synthetic histogranin (10-100 nmol) in mice protect them against N-methyl-D-aspartate (NMDA)-induced convulsions without affecting convulsions induced by (R,S)-alpha-amino-3-hydroxy -5-methyl-4-isoxazole-propionate (AMPA), kainate and bicuculline. The peptide also binds to specific sites on human peripheral blood mononuclear cells and it evokes the release of tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6) from isolated rat macrophages in culture. Since the structure of histone H4 is considered as one of the most conservative, it is presumed that histogranin possesses its own precursor and that its gene is distinctly expressed.

Adjuvants, Immunologic↗

PubMed1995

N-methyl-D-aspartate receptor antagonist activity and phencyclidine-like behavioral effects of the pentadecapeptide, [Ser1]histogranin.

The behavioral and pharmacologic profiles of [Ser1]histogranin ([Ser1]HN) were assessed by monitoring its ability to displace the binding of the specific N-methyl-D-aspartate (NMDA) receptor ligand, [3H]CGP 39653, to block the convulsant effects of NMDA and other excitatory agents in mice, and to produce phencyclidine (PCP)-like behavioral effects in rats. The peptide potently inhibited [3H]CGP 39653 binding to membrane preparations of rat brain with an IC50 of 198 nM and a maximal inhibition of 34% of the specific binding activity. Saturation binding experiments with [3H]CGP 39653 in the absence and presence of [Ser1]HN (2 microM) indicated that the inhibitory effect of the peptide was noncompetititive, producing a decrease in the maximal number of binding sites (Bmax of 62.5 fmol/mg protein as compared with 91.3 fmol/mg protein in control), but no significant change in the affinity (Kd of 4.5 nM as compared with 5.1 nM in control). Intracerebroventricular (ICV) injection of [Ser1]HN (10-100 nmol) in mice evoked a dose-dependent and selective blockade of NMDA-induced convulsions. In rats, [Ser1]HN (2.5-100 nmol, ICV) produced dose-dependent stereotypy, ataxia, and locomotion similar to those observed with PCP, at doses ranging between 50 and 400 nmol. The data indicate that [Ser1]HN noncompetitively interacts with the NMDA receptor, an action that goes along with its in vivo NMDA receptor antagonist activity and PCP-like behavioral effects.

2-Amino-5-phosphonovalerate↗

PubMed1995

Inhibitory effects of dynorphin-A on norepinephrine uptake by cardiac synaptosomal-mitochondrial fractions.

The effect of dynorphin A-(1-13) (Dyn A-(1-13)) on [3H]norepinephrine ([3H]NE) uptake was examined in cardiac synaptosomal-mitochondrial fractions of control rats (Wistar, WR; Wistar-Kyoto, WKY) and spontaneously hypertensive rats (SHR). In adult WR, Dyn A-(1-13) caused naloxone-insensitive dose-dependent inhibition of [3H]NE uptake with an IC50 of 4.0 microM. The nonopioid Dyn A fragments Dyn A-(2-13) and Dyn A-(6-10) displayed 89 and 11% of the potency of Dyn A-(1-13), respectively, whereas Dyn A-(1-8), Leu-enkephalin, and the selective opioid agonists [D-Ala2, N-MePhe4, Glyol5]enkephalin (DAGO, mu), [D-Ser2, Thr6]Leu-enkephalin (DSLET, delta), and U-50488H (kappa) were inactive. The relative potency of various analogues and fragments of Dyn A in inhibiting [3H]NE uptake correlated well (r = 0.96) with their potency in inhibiting binding of [3H]Dyn A-(1-13) to nonopioid sites on cardiac membrane preparations. Dyn A-(1-13) showed the same potency in inhibiting [3H]NE uptake in prehypertensive (4-week-old) SHR as in age-matched WR and WKY. However, at ages 8 and 16 weeks Dyn A-(1-13) was twice as potent in SHR as in WR and WKY. The increased inhibitory potency of Dyn A-(1-13) in 8-week-old SHR was accompanied by a 1.3-fold increase in number of cardiac nonopioid [3H]Dyn A-(1-13) binding sites. Dyn A and related peptides inhibit [3H]NE uptake by cardiac synaptosomes by a nonopioid mechanism. The possible involvement of such a mechanism in development of hypertension in SHR is discussed.

Animals↗

PubMed1995

Synthesis and biological activity of histogranin and related peptides.

Histogranin (HN) was first isolated from bovine adrenal medulla and shown to be a pentadecapeptide displaying N-methyl-D-aspartate (NMDA) receptor antagonist activity. To determine the active pharmacophore of HN, fragments of the peptide were synthesized and their structure-activity relationships studied by measuring their ability to displace the binding of [125I][Ser1]HN to rat brain membrane preparations and to block NMDA-induced convulsions in mice. In the binding assay, only the full length peptide HN and HN(1-10) displayed a high affinity (Ki of 72 and 162 nM, respectively). All other tested fragments with deletions at the N- and (or) C-terminals of the molecule showed large (16- to 2500-fold) decreases in potency. The least active peptide fragment tested was HN(6-10) (Ki of 164 microM). In vivo, HN and HN(2-15) (100 nmol; i.c.v.) produced 94 and 40% protection against NMDA-induced convulsions in mice, respectively. None of the other peptide fragments displayed significant anticonvulsant activity. The protective activity of HN (60 and 100 nmol) was markedly antagonized by coadministration of HN(1-10) (100 nmol). The results indicate that the in vivo anti-NMDA and in vitro binding activities of HN and related peptides, with the exception of HN(1-10), depend upon the integrity of the molecule. On the other hand, the high affinity of HN(1-10) for HN binding sites correlates well with its antagonist effects towards the activity of the parent peptide.

Animals↗

PubMed1995

Tetrodotoxin-sensitive Ca2+ and Ba2+ currents in human atrial cells.

A tetrodotoxin (TTX)-sensitive fast inward Ca2+ current (ICa,TTX) was recorded at physiological Ca2+ levels (2 mM) in human single atrial cells. The whole-cell patch-clamp method and Na(+)-free solutions (20-22 degrees C) were used. ICa,TTX depended upon extracellular Ca2+. It was prominent at rather negative test potentials (maximal peak amplitude at approximately -40 mV) and was observed only at holding potentials lower than -80 mV. It had the same size and kinetics when Ca2+ was exchanged for Ba2+ as the charge carrier. Its rapid activation and inactivation kinetics, voltage-dependent availability and fast recovery from inactivation resembled that of the Na+ currents (INa). ICa,TTX was insensitive to 250 microM Ni2+ and 10 microM La3+, both known to block totally T-type ICa (not evidenced here). ICa,TTX was suppressed by Na+ channel inhibitors such as TTX (10 microM) and Cd2+ (20 microM) and its decay was slowed by the specific Na+ channel activator veratrine (200 micrograms/ml). We found that both time to peak and time-constant of inactivation of ICa,TTX were slower than that of INa. There was no correlation between the presence and size of ICa,TTX and that of INa. In conclusion, ICa,TTX may reflect the presence and activation of either Ca(2+)-conducting channels related to Na+ channels or, alternatively, of a fraction of Na+ channels with an increased permeability for Ca2+ and Ba2+ ions.

Atrial Function↗

PubMed1994

Dynorphin potentiation of [3H]CGP-39653 binding to rat brain membranes.

Dynorphin A-(1-13) and related peptide fragments were tested for their ability to modulate the binding of the competitive NMDA receptor antagonist, [3H]2-amino-4-propyl-5-phosphono-3-pentanoic acid ([3H]CGP-39653), to rat brain membranes. Dynorphin A-(1-13) produced a dose-dependent (1 nM to 10 microM) potentiation of [3H]CGP-39653 binding. The potentiation was insensitive to the kappa-opioid receptor antagonist norbinaltorphimine and it was also observed with the non-opioid peptides dynorphin A-(2-13) and dynorphin A-(6-10). Among various compounds which interact with distinct sites on the NMDA receptor complex, glycine (Gly; 1 microM) and the Gly receptor antagonist, (+/-)-3-amino-1-hydroxy-2-pyrrolidone ((+/-)-HA-966; 10 microM), blocked the dynorphin A-(1-13) induced potentiation of [3H]CGP-39653 binding. In equilibrium binding experiments, dynorphin A-(1-13) (10 microM) caused a significant increase in the binding capacity (Bmax) of [3H]CGP-39653 (from 111 to 306 fmol/mg protein) but not change in the apparent dissociation constant (Kd of 8.5 nM as compared with 8.7 nM in the absence of the peptide). The results indicate that dynorphin A and related peptides modify the expression of [3H]CGP-39653 binding sites consecutive to a non-opioid interaction with the NMDA receptor complex.

2-Amino-5-phosphonovalerate↗

PubMed1994

Agonist and antagonist opioid activity of axial and equatorial conformations of S-methyl- and S-allyl-morphinans.

Resolved axial (beta) and equatorial (alpha) forms of S-methyl (beta-sulforphanol, alpha-sulforphanol) and S-allyl (beta-sulfallorphan, alpha-sulfallorphan) morphinans were tested for their ability to depress the electrically evoked contractions of the guinea pig ileum and of the mouse vas deferens, to compete with the binding of prototype ligands selective for mu-, delta-, and kappa-opioid receptors in membrane preparations of rat brain and guinea pig cerebellum and to produce analgesia in a rat thermal pain assay. beta-Sulforphanol was more potent than alpha-sulforphanol in the guinea pig ileum (relative potencies of 93% and 29% respectively, as compared with levorphanol). beta-Sulfallorphan and alpha-sulfallorphan were both inactive in the guinea pig ileum assay. In the mouse vas deferens preparation, beta-sulforphanol and alpha-sulforphanol had relative potencies of 2.1% and 1.2% as compared with levorphanol, respectively, while the S-allyl derivatives were inactive. All morphinan derivatives displayed marked binding selectivity for mu-opioid receptors but alpha-sulfallorphan also showed significant binding potency on delta-opioid receptors (12% as compared to levorphanol). The compounds were also tested for their ability to antagonize the biological activity of morphine. In the guinea pig ileum, alpha-sulfallorphan potently inhibited morphine with a Ke value of 41.7 nM. alpha-Sulforphanol also antagonized morphine but with a smaller potency (Ke = 350 nM). In the mouse vas deferens, no antagonist activity against morphine was observed with any morphinan derivative tested at 1 microM. In the rat thermal pain assay, beta-sulforphanol (intracisternally, i.c.) was more potent than alpha-sulforphanol in producing analgesia while the other morphinan derivatives were inactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Interaction of histogranin and related peptides with [3H]dextromethorphan binding sites in rat brain.

Histogranin (HN) and related peptides were tested for their ability to modulate the binding of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, [3H]dextromethorphan ([3H]DM), to rat brain membranes. HN, [Ser1]HN and the C-terminal fragment HN-(6-15) (0.1 nM-1 microM) potentiated (up to 1.6-fold) the binding of [3H]DM (5 nM) whereas the N-terminal fragment HN-(1-10) had no effect. The potentiation of [3H]DM binding by [Ser1]HN was blocked by NMDA (100 microM) and the NMDA receptor antagonist, CPP (1 microM) but not by the sigma (sigma) receptor ligand, (+)-pentazocine (0.1 microM) and the phencyclidine (PCP) receptor ligand, TCP (1 microM). Equilibrium binding experiments in presence of TCP (1 microM) to block PCP receptors indicated that [Ser1]HN (1 microM) causes a significant increase in the binding capacity (Bmax) of [3H]DM (from 2.46 to 3.46 pmol/mg protein) but no change in the apparent dissociation constant (Kd of 428 nM as compared with 487 nM). The results indicate that HN and related peptides specifically enhance the number of [3H]DM binding sites associated to the NMDA receptor complex.

Animals↗

PubMed1994

Expression of beta 1-6-branched N-linked oligosaccharides is associated with activation in human T4 and T8 cell populations.

Activation of human T lymphocytes by phorbol 12-myristate 13-acetate and leukoagglutinin from Phaseolus vulgaris (L-PHA) results in important changes in N-glycosylation. The most important event is the increase, in both T4 and T8 cells (especially the latter), of L-PHA+ structures characterized by beta 1-6-branching of complex-type oligosaccharides. Moreover, the existence of a CD4-mediated increase of these beta 1-6-branched structures on positively selected T4 cells, as compared with the negatively selected ones, suggests that the presence of these structures, not detectable on T8 resting cells, could be related to stimulation events triggered by both selection methods. This beta 1-6-branching on N-glycans, strongly associated with a metastatic phenotype in human and rodent tumors, is exhibited by numerous glycoproteins on stimulated cells, as shown by blot analysis.

Antigens, CD↗

PubMed1994

Up-regulation of cytokine production in alveolar macrophages by histogranin, a novel endogenous pentadecapeptide.

Recently, histogranin (HN), a newly found pentadecapeptide, was shown to enhance tumor necrosis factor (TNF) production by alveolar macrophages (AM). In this study, we have investigated whether HN was present in tissues rich with immune cells and further explored the effect of HN and [Ser1]HN on the production of TNF and other key cytokines. Relatively high levels of immunoreactive (ir)-HN were found in rat lung (14.9 pmol/g) and spleen (12.3 pmol/g), indicating its localization in close proximity to macrophages/monocytes and lymphocytes. Furthermore, HN and [Ser1]HN (10(-8)-10(-7) M) stimulated basal and lipopolysaccharide (LPS)-induced interleukin 1 (IL-1) mRNA expression and IL-1 release from rat AM. [Ser1]HN also stimulated basal and LPS-induced interleukin-6 (IL-6) release. Although HN did not affect the kinetics of cytokine production, the maximal enhancing effect of HN was seen at 3 h for TNF, 6 h for IL-1 and 18 h for IL-6. These data indicate that HN can up-regulate a cytokine cascade involving TNF, IL-1 and IL-6 and suggest a role for this endogenous peptide in immune regulation.

Animals↗

PubMed1994

Non-opioid effects of dynorphins: possible role of the NMDA receptor.

Dynorphin A (dynA) and related opioid peptides produce moderate analgesic effects with restricted types of pain stimuli that are often accompanied by a large variety of naloxone-insensitive biochemical and behavioural effects. In binding assays in vitro, dynA possesses a high affinity for mu-, delta- and kappa- opioid receptors with some selectivity for kappa sites, but it also binds to specific non-opioid sites. The involvement of the NMDA receptor has been suggested to explain some of the non-opioid effects of dynA and related peptides. In this article, Vijay Shukla and Simon Lemaire review the experimental evidence that suggests a role for the NMDA receptor in some of the pharmacological effects of dynA and related peptides.

Amino Acid Sequence↗

PubMed1993

Characterization of histogranin receptors in human peripheral blood lymphocytes.

Histogranin (HN), a peptide recently isolated from bovine adrenal medulla, is also present in the spleen. In present studies, specific high affinity binding sites for HN were characterized on membrane preparations of human lymphocytes by radioligand binding. [125I]-[Ser1]HN binding was found to be dependent on time and protein concentration and to be sensitive to trypsin treatment. The binding displayed high affinity (Kd = 1.1 +/- 0.3 nM) and saturability (Bmax = 40.2 +/- 5.0 fmol/mg protein), and it was reversed upon addition of unlabelled [Ser1]HN and closely related peptides. The relative potency of various fragments in displacing [125I][Ser1]HN binding indicated that the active core of the molecule resides inside the C-terminal fragment, HN-(6-15). Interestingly, depressed patients displayed a marked decrease in the binding activity (from 15.4 to 8.55 fmol/mg protein at 0.5 nM of [125I][Ser1]HN). The presence of high affinity HN binding sites on lymphocytes provides evidence for a modulatory role for HN in the regulation of lymphocyte functions.

Adult↗

PubMed1993

Isolation and characterization of histogranin, a natural peptide with NMDA receptor antagonist activity.

Histogranin, was co-purified with bombesin-like immunoreactive peptides from bovine adrenal medulla. Its structure, H-Met-Asn-Tyr-Ala-Leu-Lys-Gly-Gln-Gly-Arg-Thr-Leu-Tyr-Gly-Phe-COOH, was determined by gas-phase Edman degradation. It was in accordance with its amino acid composition and corresponded to a 15 amino acid fragment (fragment 86-100) of histone H4 with substitutions in positions 1 (Val), 2 (Val) and 7 (Arg). The peptide was synthesized by the solid-phase procedure and the synthetic product was identical to the natural peptide as determined by its retention time on three analytical high-performance liquid chromatography systems. An antibody was raised against synthetic [Ser1]histogranin and used to monitor the presence of histogranin in various rat tissues and subcellular fractions of bovine adrenal medulla. In rats, immunoreactive histogranin was mainly concentrated in the pituitary (5065 pmol/g) and the adrenal glands (268 pmol/g), but it was also present in other tissues including the brain (1.6 pmol/g) and blood plasma (24 fmol/ml). A neuropeptide function for the adrenal peptide was suggested by its relative high concentration in chromaffin granules (42 fmol/mg protein as compared with 1 fmol/mg protein in cytosol) and its release from perfused bovine adrenal glands. In rat brain membrane preparations, synthetic histogranin displaced the binding of [3H]CGP 39653, a specific ligand of N-methyl-D-aspartate (NMDA) receptor. The displacement curve was biphasic with IC50 of 0.6 and 3955 nM, representing 33% and 67% of the binding sites, respectively. Intracerebroventricular (i.c.v.) injection of the peptide (5-100 nmol) in mice produced a dose-dependent protection against NMDA (0.5-1.0 nmol) -induced convulsions but not against (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA, 0.25-2.0 nmol), kainate (0.25-0.75 nmol) and bicuculline (1-10 nmol)-induced convulsions. These results suggest that histogranin may be an endogenous modulator of NMDA receptor functions.

2-Amino-5-phosphonovalerate↗

PubMed1993

Norbinaltorphimine protection against N-methyl-D-aspartic acid-induced convulsions and mortality.

The kappa-selective opioid antagonist, norbinaltorphimine (Nor-BNI), was tested against convulsions and mortality induced by the excitatory amino acids, N-methyl-D-aspartic acid (NMDA), (R,S)-alpha-amino-3- hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainic acid and the gamma-aminobutyric acid antagonist, bicuculline. Nor-BNI (10-40 nmol; intracerebroventricularly, i.c.v.) protected against NMDA (0.5-2.0 nmol i.c.v.)-induced convulsions and NMDA (2 nmol i.c.v.) and AMPA (2 nmol i.c.v.)-induced mortality. The opioid antagonist, naloxone (10 nmol i.c.v.), had no protecting activity. In vitro, Nor-BNI competed with the binding of the specific NMDA receptor ligand, [3H]D,L-(E)-2-amino-4-propyl- 5-phosphono-3-pentenoic acid ([3H]CGP 39653, 10 nM; IC50 of 1.63 +/- 0.20 microM) to mouse brain membrane preparations. The results indicate that the protecting activities of Nor-BNI are mediated by NMDA receptor-related mechanisms.

2-Amino-5-phosphonovalerate↗

PubMed1993

Characterization of non-opioid [3H]dynorphin A-(1-13) binding sites in the rat heart.

The binding characteristics of [3H]Dynorphin A-(1-13) ([3H]Dyn A-(1-13) were examined in membrane preparations of rat heart. Saturation binding studies with increasing concentrations between 2.5 and 500 nM indicated that [3H]Dyn A-(1-13) binds to a single population of sites with a Kd of 285 nM and a Bmax of 215 pmol/mg protein. [3H]Dyn A-(1-13) binding is sensitive to trypsin treatment and it is inhibited by Zn2+ and Mg2+ with IC50 values of 159 and 310 microM, respectively. Dyn A and related peptides competes with the binding of [3H]Dyn A-(1-13) with the following order of potency: Dyn A-(1-13) > Dyn A > Dyn B > alpha-neo-endorphin > Dyn A-(1-8). The non-opioid peptides Dyn A-(2-13), Dyn A-(3-13) and Dyn A-(5-13) are as potent (Ki of 0.35, 0.44 and 0.59 microM, respectively) as Dyn A-(1-13) (Ki of 0.36 microM) in inhibiting [3H]Dyn A-(1-13) binding while Leu-enkephalin (Leu-Enk) exhibits no inhibitory effect at 100 microM. Selective ligands for kappa (kappa: U-50,488H, U-69,593), mu (mu: [D-Ala2, MePhe4, Glyol5]Enk) and delta (delta: [D-Ser2, Thr6]Leu-Enk) opioid receptors as well as for phencyclidine (PCP: MK-801, TCP) and sigma (sigma: (+)-SKF-10047, DTG, 3(+)-PPP) receptors show little or no inhibition of [3H]Dyn A-(1-13) binding at 100 microM. These results indicate that the heart contains a low affinity high capacity binding site for Dyn A and related peptides, distinct from opioid, PCP and sigma receptors.

Animals↗

PubMed1993

Characterization of [125I][Ser1]histogranin binding sites in rat brain.

The binding characteristics of histogranin (HN), an endogenous peptide first recognized for its antagonism of N-methyl-D-aspartate (NMDA) responses, were determined in membrane preparations of rat brain. [125I][Ser1]HN, a stable bioactive analog of HN, bound specifically and reversibly to a homogenous population of high-affinity sites with a Kd of 25 nM and a Bmax of 410 fmol/mg protein. The binding of [125I][Ser1]HN increased linearly with membrane protein concentration and was destroyed upon membrane pretreatment with trypsin. The binding displayed rapid association and dissociation kinetics and was blocked by peptides possessing close homology with HN in the following order: [Ser1]HN-(1-15) > HN > [Ser1]HN-(1-14) > HN-(2-15) > [Ser1]-HN-(1-10) > HN-(6-10). Unrelated peptides such as substance P, beta-endorphin, neuropeptide Y, [Met5]enkephalin, [Leu5]enkephalin, dynorphin A(1-13) and neuromedin C were inactive in competition binding assays against [125I]Ser1]HN. Ligands of the binding domains of the NMDA receptor, such as (+)3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, (+) 5-methyl-10,11-dihydro 5H-dibenzo[a, d]cyclohepten-5,10-imine hydrogen maleate, 1-N-(2-thienyl)cyclohexylpiperidine, glycine and glutamate were also ineffective in competing for [125I][Ser1]HN binding sites. Interestingly, specific ligands for the polyamine site on the NMDA receptor, as well as the cations Mg++ and Zn++ inhibited [125I][Ser1]HN binding. The polyamine antagonist diethylenetriamine produced a noncompetitive inhibition with an IC50 (175 nM) comparable to that of HN (75 nM). The cations Zn++ and Mg++ displaced [125I][Ser1]HN binding with IC50 values of 18 and 240 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Selective involvement of kappa opioid and phencyclidine receptors in the analgesic and motor effects of dynorphin-A-(1-13)-Tyr-Leu-Phe-Asn-Gly-Pro.

Dynorphin A-(1-13)-Tyr-Leu-Phe-Asn-Gly-Pro (Dyn Ia; 1-8 nmol) injected intracerebroventricularly in the mouse produces two independent behavioral effects: (1) a norbinaltorphimine (kappa opioid antagonist)-reversible analgesia in the acetic acid-induced writhing test and (2) motor dysfunction characterized by wild running, pop-corn jumping, hindlimb jerking and barrel rolling and antagonized by the irreversible phencyclidine (PCP) and sigma (sigma) receptor antagonist, metaphit and the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, dextromethorphan and ketamine. The specific involvement of the PCP receptor in the motor effects of Dyn Ia is supported by the direct competitive interaction of the peptide with the binding of [3H]MK-801 (Ki: 0.63 microM) and [3H]TCP (Ki: 4.6 microM) to mouse brain membrane preparations.

Amino Acid Sequence↗

PubMed1992

Increased preproenkephalin A gene expression in the rat heart after induction of a myocardial infarction.

The expression of preproenkephalin A (ppENK) gene was investigated in the rat heart, following the onset of myocardial infarction induced by ligation of the left anterior descending coronary artery. The relative abundance of ppENK mRNA and the level of enkephalins were measured by Northern blot analysis and radioimmunoassay, respectively, in the ventricles from control-unoperated, sham-operated, and operated rats. Three hours after the surgery, a comparison between rats with infarction and sham-operated rats revealed that the relative abundance of ppENK mRNA and the level of enkephalins were increased three- to four- and two- to three-fold, respectively, in the ventricles of rats with infarction. No difference was observed between rats with infarction and sham-operated rats 24 h after the surgery, or between rats with infarction compared at time intervals of 3 and 24 h following the surgery. The abundance of the ppENK mRNA in the polysomal fraction of the ventricular septum was also measured 3 h after the surgery and found to be threefold higher in rats with infarction as compared with sham-operated rats. These results indicate that the level of enkephalins rapidly increases in the ventricles of rats following myocardial infarction, and that this higher level may be ascribed to a stimulation of the local synthesis of enkephalins.

Animals↗