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Biomedical subjects

J Rossier

Publications and source records attributed to J Rossier.

At least 163 records · Page 9Linked to original sources
PubMed1984

[Potent convulsant effects of a benzodiazepine inverse agonist, methyl beta-carboline-3-carboxylate in cats].

The convulsant properties of methyl beta-carboline-3-carboxylate (beta-CCM), which is a homologue of a putative benzodiazepine receptor ligand in the mammalian central nervous system, were examined in cats. Subcutaneous injection of 0.5 mg/kg of the beta-CCM produced various degrees of myoclonic jerks always accompanied by cortical spike burst. Some autonomic symptoms such as tachypnea, hypersecretion of thick mucous saliva, vomiting and mydriasis were also presented. Subcutaneous injection of 1.0 mg/kg of the compound induced a generalized tonic-clonic convulsion. Injection of the same amount of the drug 1 hour later in the same cats failed to provoke a generalized seizure. Repeated injection of the same dose 3 hours later provoked a generalized seizure, but with a longer latency. However, repetition of the experiments 24 hours after or 10 days after the first injection consistently induced the same type of generalized seizure with the same latency as the first injections. These results support the suggestion that the pharmacological effect, especially the convulsive effect, of beta-CCM is dose-related, reversible and reproducible in the same cats and among different cats. Moreover, the postictal refractory period in this model of epilepsy may continue about for 3 hours.

Animals↗
PubMed1983

The partial benzodiazepine agonist properties of Ro 15-1788 in pentylenetetrazol-induced seizures in cats.

The effects of Ro 15-1788, a specific benzodiazepine antagonist, were studied on pentylenetetrazol-induced seizures in cats. Ro 15-1788 decreased the number of myoclonic jerks induced by a subconvulsive dose of pentylenetetrazol (12.5 mg/kg, i.m.). Ro 15-1788 suppressed generalized convulsive seizures induced by a minimal convulsive dose of pentylenetetrazol (25-35 mg/kg), but did not block the effects of higher doses (35-45 mg/kg). These results indicate that Ro 15-1788 is not a pure benzodiazepine antagonist, but has partial agonistic properties.

Animals↗
PubMed1983

The heptapeptide Met-enkephalin-Arg6, Phe7 is released from rat striatum in vitro by high potassium.

We present evidence that the heptapeptide Met-enkephalin-Arg6, Phe7 is released from rat striatal slices following depolarization by a high concentration of KCl. The heptapeptide-immunoreactive material released in the incubation medium, which is shown by HPLC and radioimmunoassay of serial dilutions to represent authentic heptapeptide, is detectable in the incubation media only in the presence of a cocktail of peptidase inhibitors containing thiorphan (0.1 microM), captopril (1 microM) and bestatin (20 microM).

Animals↗
PubMed1983

Convulsions induced by submaximal dose of pentylenetetrazol in mice are antagonized by the benzodiazepine antagonist Ro 15-1788.

The effects of benzodiazepine antagonist Ro 15-1788, alone or with diazepam, were studied in mice on convulsions induced by pentylenetetrazol (PTZ). We found that Ro 15-1788 (1 mg/kg) was able to antagonize the anticonvulsive effects of diazepam (1 mg/kg), but also had, with submaximal doses of PTZ (65 mg/kg), its own anticonvulsive action. At very low doses (0.1 mg/kg), it even potentiated the anticonvulsive effects of diazepam (0.05 mg/kg). This dual action provides evidence for partial agonist properties of the antagonist Ro 15-1788.

Animals↗
PubMed1983

A Met-enkephalin-containing-peptide, BAM 22P, as a novel substrate for glandular kallikreins.

Homogeneous preparations of two well-characterized glandular kallikreins have been examined for their ability to hydrolyze BAM 22P, a methionine-enkephalin-containing-peptide found in the adrenal medulla. Both enzymes cleaved preferentially the Arg6-Arg7 bond in this substrate. The specificity constant (kcat/Km) for this cleavage was 86 mM-1 sec-1 for horse urinary kallikrein and 566 mM-1 sec-1 for porcine pancreatic kallikrein. These results demonstrate a previously undescribed specificity for glandular kallikreins and suggest a possible role for these widely distributed enzymes in prohormone processing.

Animals↗
PubMed1983

Presence in brain of synenkephalin, a proenkephalin-immunoreactive protein which does not contain enkephalin.

The primary sequence of adrenal proenkephalin has recently been reported by three groups who have isolated and sequenced the cDNA for this prohormone. Several intermediates in the processing of proenkephalin, containing from one to four copies of [Met] enkephalin, have been purified from the adrenal medulla. Although there is evidence that the proenkephalin is identical in the brain and the adrenal medulla, similar intermediates have not been isolated from brain. We report here the production of an antiserum directed against a purified enkephalin precursor derived from the amino terminus of adrenal proenkephalin which cross-reacts with an antigen in brain. The immunoreactive protein in brain does not contain the sequence of enkephalin, but shows a pattern of distribution in immunohistochemical studies parallel to that of the enkephalins. In extracts of bovine caudate-putamen, this antigen is present in a molar concentration approximately one-fifth of that of [Met] enkephalin. The results demonstrate that the antiserum recognizes antigenic determinants within the N-terminal 72 amino acid residues of adrenal proenkephalin and that the enkephalin precursor in brain is similar to that found in the adrenal medulla. Furthermore, the absence of the enkephalin sequence in the brain protein indicates that concentrations of the larger intermediates in the processing of proenkephalin are much lower in the brain than in the adrenal medulla.

Adrenal Medulla↗
PubMed1983

Anxiogenic and non-anxiogenic benzodiazepine antagonists.

Benzodiazepines are widely used anxiolytic and anticonvulsant drugs, and brain receptors for these drugs have been characterized by Möhler and Okada and Squires and Braestrup. Recently, substances that antagonize benzodiazepine binding to brain receptors have been discovered. These benzodiazepine antagonists were shown to block the central effects of benzodiazepines and particularly their anticonvulsive properties. Two such antagonists, Ro 15-1788 (an imidazodiazepine) and methyl beta-carboline-3-carboxylate (beta-CCM), have recently been shown to have different intrinsic pharmacological properties. beta-CCM, injected into baboons, cats, mice and rats, is a convulsant, whereas Ro 15-1788 lacks such an activity. Thus, the separation of convulsant and non-convulsant antagonists has been proposed. We suggest here that a subclassification of antagonists is also valid at the behavioural level, based on a conflict model in mice. We show that Ro 15-1788 and beta-CCM antagonize the anxiolytic effect of benzodiazepines. In addition, we find that, when injected alone, Ro 15-1788 has no anxiogenic effects while beta-CCM has anxiogenic properties. We therefore propose that beta-CCM is an anxiogenic convulsant benzodiazepine antagonist and that Ro 15-1788 is a non-anxiogenic non-convulsant benzodiazepine antagonist.

Animals↗
PubMed1983

Plasma immunoreactive beta-endorphin levels in depression. Effect of electroconvulsive therapy.

Immunoreactive (ir) plasma beta-endorphin level was assayed in ten symptomatic patients with a unipolar major depressive disorder and in 16 psychiatrically normal controls matched for age and sex. Plasma ir-beta-endorphin level in depressed patients was similar to that in controls. All depressed patients was similar to that in controls. All depressed patients had a transient, approximately threefold increase in ir-beta-endorphin after each use of electroconvulsive therapy (ECT). The increase of plasma ir-beta-endorphin level after ECT parallels the transient elevation of adrenocorticotropic hormone level reported by others and probably reflects a hypothalamic response to ECT.

Adrenocorticotropic Hormone↗
PubMed1983

Co-release of enkephalins and precursors with catecholamines by the perfused cat adrenal in-situ.

In the present study we have carefully determined the nature and amount of enkephalin immunoreactive product co-related with catecholamines by the cat adrenal gland perfused in-situ. Met-enkephalin immunoreactivity (IR) and total Met-enkephalin-IR obtained after digestion of large enkephalin containing peptides were released by electrical stimulation of the splanchnic nerves, with 0.1 mM acetylcholine perfusion or 50 mM K+. We have found that in response to splanchnic nerve stimulation 47% of enkephalinergic material was on the form of small peptide (Met-enkephalin, Leu-enkephalin, heptapeptide, octapeptide). When drastic stimuli like perfusion with 50 mM or 0.1 mM acetylcholine were used, the bulk of the enkephalinergic material was present on the form of large fragments of the precursor. These results are interpreted as follows: when physiological stimuli are used, mature granules containing fully processed precursor are released; when drastic chemical stimuli are applied, unmature granules containing partially processed precursor are also released.

Adrenal Glands↗
PubMed1983

Purification of the N-terminal fragment of proenkephalin from bovine adrenal medulla.

Two forms of the N-terminal fragment of proenkephalin have been purified from the bovine adrenal medulla and characterized. One of these proteins contains the sequence of Met-enkephalin and is composed of residues 1-77 of proenkephalin. The other protein does not contain Met-enkephalin and is composed of residues 1-72 of proenkephalin.

Adrenal Medulla↗
PubMed1983

Release of the heptapeptide Met-enkephalin-Arg6-Phe7 and of the octapeptide Met-enkephalin-Arg6-Gly7-Leu8 from rat striatum in vitro and their rapid inactivation.

The heptapeptide Met-enkephalin-Arg6-Phe7 (MERF) and the octapeptide Met-enkephalin-Arg6-Gly7-Leu8 (MERGL) are potent opioid peptides present in the sequence of proenkephalin, the common precursor of Met- and Leu-enkephalin (ME and LE). We demonstrate that MERF and MERGL are released concomitantly with ME and LE from rat striatal slices following a depolarisation by K+. This release is a Ca2+-dependent process. While the ratios of ME to LE, MERF and MERGL found in the tissue (ME/LE = 2.6; ME/MERF = 3.1; ME/MERGL = 4.5) are in good agreement with the ratios found in the proenkephalin molecule (ME:LE:MERF:MERGL = 4:1:1:1), the amounts of MERF and MERGL recovered from the medium are low compared to those of ME and LE, suggesting a rapid degradation of released MERF and MERGL. In fact, when incubated with striatal slices, (3H-Tyr)-MERF is rapidly degraded by four classes of peptidases: the "enkephalinase", the angiotensin-converting enzyme (ACE), aminopeptidase(s) and an endopeptidase releasing the tetrapeptide Tyr-Gly-Gly-Phe (YGGF). Whereas the activities of the three former peptidases are reduced or abolished in the presence of thiorphan (0.1 microM), captopril (1 microM) and bestatin (20 microM), the amount of YGGF formed by the endopeptidase is not reduced in these conditions but actually increased.

Animals↗
PubMed1983

Enkephalins are associated with adrenergic granules in bovine adrenal medulla.

The subcellular localization of enkephalins was studied in the bovine adrenal medulla. In the adrenal medulla enkephalins (Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg6-Phe7 and Met-enkephalin-Arg6-Gly7-Leu8) are found free and in the form of cryptic peptides included in larger precursors. Total Met-enkephalin immunoreactivity, which includes free and cryptic peptides, was determined after a sequential enzymatic treatment with trypsin and carboxypeptidase B. Total Met-enkephalin immunoreactivity, dopamine beta-hydroxylase and catecholamines were found to have a parallel distribution in the various subcellular fractions. The bulk of the total Met-enkephalin immunoreactivity (42%) was recovered in the large granule fraction. The large granule fraction also contained 38% of the total dopamine beta-hydroxylase activity, and 42% of the total catecholamines. Enkephalins are thus concentrated in the chromaffin granules. Chromaffin granules were also separated according to the method of Terland & coworkers into two fractions: one containing the dense noradrenergic vesicles and the other containing lighter adrenergic vesicles. Total Met-enkephalin immunoreactivity was restricted to the fractions containing the lighter adrenergic vesicles. In these fractions the molar ratio of adrenaline to total Met-enkephalin immunoreactivity was 97. This study is in accord with immunocytochemical observations which have indicated that enkephalins are located in adrenergic and not in the noradrenergic cells in the bovine adrenal medulla.

Adrenal Medulla↗
PubMed1983

Proenkephalin, [Met]enkephalin, and oxytocin immunoreactivities are colocalized in bovine hypothalamic magnocellular neurons.

The distribution of proenkephalin and [Met]enkephalin immunoreactivities in the bovine hypothalamo-neurohypophyseal system was studied by use of specific antisera. Proenkephalin and [Met]enkephalin immunoreactivities were found in magnocellular neuronal cell bodies in the dorsal part of the supraoptic nuclei and in the peripheral part of the paraventricular nuclei. A densely staining network of nerve terminals was found in the external part of the median eminence and in the posterior hypophysis. This general distribution is identical to that of the neurohypophyseal hormone oxytocin. The precise localization of proenkephalin and [Met]enkephalin immunoreactivities was compared to the distribution of oxytocin and vasopressin in serial 5-micron sections through the magnocellular nuclei. Oxytocin immunoreactivity was nearly always present in cells that were stained with proenkephalin and [Met]enkephalin antisera. The vasopressin-immunoreactive cells were never stained with either the proenkephalin or the [Met]enkephalin antisera.

Animals↗
PubMed1983

The enkephalinergic neuron: implications of a polyenkephalin precursor.

The study of the biochemical and physiological functions of the enkephalinergic cell has greatly extended our understanding of peptidergic cells in general. In the adrenal gland, the major part of the proenkephalin-derived peptides is present as intermediates in the processing of the precursor. These peptides are contained within the adrenergic chromaffin granules, from which they are released in response to stimulation of the cell. The nature of the products released depends on the nature of the stimulus, but it appears that mature granules containing completely processed peptides are preferentially released under physiological conditions. In the brain, the presence and release of the heptapeptide that comprises the carboxyl terminus of adrenal proenkephalin suggest that similar mechanisms are operating centrally. The identity of brain and adrenal proenkephalin is further supported by the purification from brain of a large fragment of the proenkephalin molecule, synenkephalin , and the occurrence in brain of this and the other proenkephalin-derived peptides in a molar ratio close to that found in the sequence of the adrenal precursor. The processing of proenkephalin in brain appears to follow the classical models first proposed for peptide hormones (Steiner et al. 1980), which may thus be generalized to include peptide neurotransmitters/neuroregulators. In addition, the results presented in this paper indicate that enkephalins may be cotransmitters in at least two diverse systems. Enkephalins and catecholamines are colocalized in the adrenergic granules of the adrenal gland. In the brain, enkephalins and oxytocin are colocalized in the magnocellular neurons of the hypothalamo-neurohypophyseal oxytocinergic pathway. In both of these systems, the enkephalins are present in a molar concentration that is less than 1% of the concentration of the principal messenger. Such colocalization , coupled with the numerous active peptides that may arise from proenkephalin, suggests many elegant but complex schemes of neurotransmitter interactions. For example, release of enkephalins in the neurohypophysis may regulate oxytocin release through an action on autoreceptors of the oxytocinergic terminal. In the adrenal the coreleased enkephalins may act by regulating presynaptically the cholinergic output of the splanchnic nerve. However, further studies are needed to define clearly the physiological roles of such cotransmission . From the abundance of proenkephalin-derived peptides in the basal ganglia, it appears that enkephalins may represent the principal transmitter in some central neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Medulla↗
PubMed1983

Regional distribution of methionine-enkephalin-Arg6-Phe7 in the rat brain: comparative study with the distribution of other opioid peptides.

The distribution of the opioid peptide methionine-enkephalin-arginine6-phenylalanine7 (M-Enk-Arg6-Phe7) has been investigated in various structures of the rat brain by using a highly specific radioimmunoassay (RIA). Immunoreactive M-Enk-Arg6-Phe7 has been further characterized by high performance liquid chromatography. The levels of M-Enk-Arg6-Phe7 in various structures of the rat brain were compared with the levels of several other opioid peptides, including methionine-enkephalin (M-Enk), leucine-enkephalin (L-Enk), dynorphin 1-13, and alpha-neoendorphin, which were also measured by RIA. There was a close relationship between the distribution of M-Enk-Arg6-Phe7 immunoreactive material (ir), M-Enk ir, and L-Enk ir. The distribution of dynorphin 1-13 ir and alpha-neoendorphin ir appeared to be distinct from that of the enkephalin group. These results are in agreement with recent reports on the cloning and sequencing of the c-DNA coding for the prohormones, in which it has been hypothesized that M-Enk-Arg6-Phe7 and M-Enk are synthesized by the same precursor, called proenkephalin, and that dynorphin-related peptides and alpha-neoendorphin arise from a separate precursor, prodynorphin.

Amino Acid Sequence↗