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Biomedical subjects

Y Sarne

Publications and source records attributed to Y Sarne.

At least 55 records · Page 3Linked to original sources
PubMed1985

Demonstration of an imipramine endacoid in rat brain.

The partial purification and characterization of an imipramine endacoid from rat brain is reported. High affinity 3H-imipramine binding as well as 3H-serotonin uptake in both brain and platelet preparations is inhibited in a dose-dependent fashion by the endogenous substance. The effect of the endogenous factor appears to be specific since it does not affect the binding of other drugs to their membrane receptors. The substance is resistant to proteolytic enzymes and is unevenly distributed in rat brain being highly concentrated in the hypothalamus and striatum. Its concentration in rat brain is not changed after repeated electroconvulsive shock treatment.

Animals↗
PubMed1984

The Torpedo electric organ is a model for opiate regulation of acetylcholine release.

Acetylcholine release from the nerve terminals of the purely cholinergic Torpedo electric organ is inhibited by morphine in a dose-dependent, naloxone-reversible fashion. In addition, it is shown that this preparation contains an enkephalin-like substance which, like acetylcholine, is present in a high concentration at the nerve terminals. These findings and the chemical homogeneity of the electric organ nerve terminals render this preparation an excellent model for the study of opiate regulation of neurotransmitter release.

Acetylcholine↗
PubMed1984

Humoral-endorphin blood levels in autistic, schizophrenic and healthy subjects.

Basal morning humoral (H)-endorphin blood levels were assessed in ten autistic patients, 12 chronic schizophrenic patients and 11 healthy control subjects. Four autistic patients and four schizophrenic patients were drug free for at least 6 months while all other psychiatric patients were under treatment with antidopaminergic agents. Significantly reduced opioid levels were observed in the autistic group (827 +/- 103 vs 1121 +/- 75 pg-eq/ml, P less than 0.025), although the difference was actually only 26% of the control mean. A similar tendency toward low H-endorphin levels was also observed in the schizophrenic patients; however this difference was not significant (919 +/- 129 vs 1121 +/- 75 pg-eq/ml; NS). No significant difference was obtained between subjects suffering from the two psychiatric disorders (827 +/- 103 vs 919 +/- 129 pg-eq/ml; NS). Various interpretations of the decreased secretion of H-endorphin are discussed.

Adolescent↗
PubMed1984

Opiates inhibit acetylcholine release from Torpedo nerve terminals by blocking Ca2+ influx.

In the present communication we report that Ca2+-dependent acetylcholine release from K+-depolarized Torpedo electric organ synaptosomes is inhibited by morphine, and that this effect is blocked by the opiate antagonist naloxone. This finding suggests that the purely cholinergic Torpedo electric organ neurons contain presynaptic opiate receptors whose activation inhibits acetylcholine release. The mechanisms underlying this opiate inhibition were investigated by comparing the effects of morphine on acetylcholine release induced by K+ depolarization and by the Ca2+ ionophore A23187 and by examining the effect of morphine on 45Ca2+ influx into Torpedo nerve terminals. These experiments revealed that morphine inhibits 45Ca2+ influx into K+-depolarized Torpedo synaptosomes and that this effect is blocked by naloxone. The effects of morphine on K+ depolarization-mediated 45Ca2+ influx and on acetylcholine release have similar dose dependencies (half-maximal inhibition at 0.5-1 microM), suggesting that opiate inhibition of release is due to blockage of the presynaptic voltage-dependent Ca2+ channel. This conclusion is supported by the finding that morphine does not inhibit acetylcholine release when the Ca2+ channel is bypassed by introducing Ca2+ into the Torpedo nerve terminals via the Ca2+ ionophore.

Acetylcholine↗
PubMed1983

Somatostatin mydriasis in mice.

Administration of somatostatin intracerebroventricularly to mice produced a dose-dependent mydriasis, whereas intravenous injections were ineffective. Naloxone could prevent or abolish this effect. It is suggested that somatostatin either directly excites opiate receptors or activates endopioid pathways involved in the regulation of pupillary size.

Animals↗
PubMed1983

Analgesia induced by electroconvulsive shock: brain enkephalins may mediate tolerance but not the induction of analgesia.

Electroconvulsive shock (ECS) administered to rats produces potent analgesia. This analgesic effect displays opiate characteristics with tolerance to ECS analgesia seen with repeated induction and cross tolerance observed following the chronic administration of analgesic dose of morphine. Furthermore, tolerance development after repeated ECS application could be blocked by daily pretreatment with the long acting opiate antagonist naltrexone (5 mg/kg). In contrast to these opiate characteristics of ECS analgesia, naltrexone administration (0.5, 5 and 10 mg/kg) failed to attenuate the acute analgesic effect of ECS. Measurement of brain enkephalin levels revealed an increase in enkephalin contents after 10 daily ECS applications, an effect which was not affected by naltrexone pretreatment. Acute administration of ECS did not affect brain enkephalin levels either immediately or 24 h after ECS administration. Significant increases in brain enkephalin following chronic ECS were observed in the hypothalamus and striatum but not in the mesencephalon or hindbrain. A gradual return of enkephalin levels to baseline values was seen with days when ECS was no longer administered. Parallel behavioral studies showed that ECS analgesia also showed a gradual recovery from tolerance after discontinuation of chronic ECS. Based on these and previous studies we propose that different systems may mediate the acute analgesic effect of ECS on the one hand, and the tolerance to such an effect observed after repeated administration on the other. We further suggest that the acute action of ECS may be mediated by substances with only partial opiate characteristics, while the long term effects observed may be due to the increase in brain enkephalin contents after chronic ECS application.

Animals↗
PubMed1982

Differential effect of humoral endorphin on the binding of opiate agonists and antagonists.

Humoral (H) endorphin, a novel endogenous factor with opiate-like activity was further characterized using various radioreceptor assays. H-Endorphin displaced both labelled opiates (morphine, ethylketazocine) and opioid peptides (leucine-enkephalin) from their specific binding sites in rat brain membranes. The effect of sodium ions on H-endorphin indicates its agonistic nature which is in agreement with previous pharmacological experiments. However, H-endorphin potentiated the binding of the opiate antagonist naloxone to brain membranes. This peculiar effect of H-endorphin on naloxone, together with the non-conventional interactions observed in various pharmacological assays, clearly distinguishes H-endorphin from other opioid ligands. A multisite model of the opiate receptor is presented. This model, which is compatible with the well documented evidence for receptors heterogeneity also explains non-conventional interactions between various opioid ligands.

Animals↗
PubMed1982

Electroconvulsive shock (ECS) and H-endorphin-induced analgesia: unconventional interactions with naloxone.

Acute administration of electroconvulsive shock (ECS) has been shown previously to produce potent analgesia which is only partially reversed by naloxone but shows almost complete tolerance after both repeated ECS and chronic morphine administration. In an attempt to elucidate the underlying basis of ECS analgesia it was recently compared with the analgesic effect of a newly identified opioid, humoral (H)-endorphin. Intracerebroventricular (i.c.v.) injection of H-endorphin to rats produces a dose-related analgesic effect as measured by the tail flick method. Furthermore, 4 days of daily i.c.v. injections of 40 microgram of morphine resulted in complete tolerance to the analgesic effect of H-endorphin. However, naloxone only caused a partial reversal of H-endorphin analgesia. Surprisingly only the lower dose of 1 mg/kg exerted a significant antagonistic effect while a higher dose of 10 mg/kg of the antagonist was without effect. A similar unconventional profile of the effect of naloxone could be seen with ECS analgesia. Here, pretreatment with 1 mg/kg of naloxone significantly attenuated analgesia, whereas administration of 10 mg/kg of the antagonist was without effect. In contrast, catalepsy measured in the same animals was not affected by 1 mg/kg of naloxone but increasing the dose to 10 mg/kg produced a significant attenuation of ECS catalepsy. The opioid nature of H-endorphin analgesia on one hand and the unconventional dose relation with naloxone of both H-endorphin and ECS analgesia on the other hand, suggests the involvement of this opioid in analgesia induced by ECS. Furthermore, it is possible that other behavioral manipulations which display only partial opiate characteristics may be mediated by H-endorphin or similar endogenous substances.

Analgesia↗
PubMed1982

Differential effects of long-term electroconvulsive shock on brain levels of enkephalin and humoral-endorphin.

Electroconvulsive shock (ECS) administrations repeated for 10 consecutive days cause an elevation in the opioid content of the rat brain. Two different endogenous opioids, enkephalin and humoral-endorphin, undergo independent changes that differ in both their time course and intracerebral localization. These metabolic changes parallel long-term behavioral modifications such as the development and dissipation of tolerance to the analgesic effect of ECS. The activation of two different, independent, endogenous opioid systems by ECS is in agreement with previous behavioral and pharmacological studies.

Animals↗
PubMed1981

On the opioid nature of phencyclidine and its 3-hydroxy derivative.

Phencyclidine (PCP) and its 3-hydroxy derivative (PCP-3-OH) caused a dose-dependent, naloxone reversible inhibition of the response of the guinea pig ileum to electrical stimulation. Unlike PCP, PCP-3-OH exerted an opioid antagonistic effect in the mouse vas deferens bioassay. Whereas both compounds displayed a high affinity in displacing [3H]SKF-10047 binding to rat brain membranes, PCP-3-OH displayed a high affinity to [3H]morphine receptors also. The mediation of alpha- and mu-receptors in the opioid effects of these drugs is discussed.

Animals↗
PubMed1980

Long-term interactions between endogenous and exogenous opiates.

The in vitro biological effect of various opiates was studied in the guinea pig ileum bioassay. Besides their direct, immediate effect, certain opiates induced sensitivity changes which persisted after their removal and the complete recovery of the preparation. These specific, asymmetrical interactions may represent long-term modulation of the opiate receptor. The in vivo pharmacological implication of opiate interaction is discussed.

Animals↗
PubMed1980

Characterization of humoral endorphin.

Utilizing a radioimmunoassay (RIA) with antibodies produced against leu-enkephalin, the presence of humoral endorphin in various body fluids and tissues has been shown. Pretreatment with trichloroacetic acid (TCA) was needed in all cases in order to detect the immunoreactivity. However, both treated and untreated samples of humoral endorphin were active in the opiate receptor assay. Gel filtration on Bio-Gel P-2 as well as on Sephadex G-10 columns of human cerebrospinal fluid (CSF), amniotic fluid (AF) and blood shows that they all contain a similar material with an apparent molecular weight of 1,000-1,400 daltons. Chromatography of rat brain homogenate exhibited two peaks of immunoreactivity, one of which is probably due to enkephalins and the other to humoral endorphin. The latter fraction was found to be very stable when incubated in CSF, while its degradation in blood was slightly faster. This opioid compound inhibited the electrically stimulated contractions of the guinea pig ileum; the specificity of this action was indicated by its reversal with low concentrations of naloxone. In pregnant women, humoral endorphin levels in maternal and cord blood remains stable during pregnancy, while there is a significantly higher concentration of humoral endorphin in the amniotic fluid at mid-trimester as compared to that in term pregnancies during labor.

Amniotic Fluid↗
PubMed1980

Humoral endorphin: can in vitro experiments explain in vivo results?

Humoral endorphin, an endogenous substance isolated from brain, blood and cerebrospinal fluid, reveals non-conventional interactions with both opiate agonist (morphine) and antagonist (naloxone) in the guinea pig ileum bioassay. The opioid activity of humoral endorphin is potentiated by pretreatment of the preparation with morphine and vice versa. Naloxone, a specific opiate antagonist, interacts with humoral endorphin in a distinct manner which distinguishes it from opiates: while low concentrations of naloxone antagonize the effect of humoral endorphin, high concentrations of the antagonist are less effective and even potentiate its opiate activity. These interactions between opiate agents can be explained assuming conformational transformation of the opiate receptor. The in vitro interactions shed new light on paradoxical and conflicting results of in vivo experiments and indicate the physiological function of humoral endorphin.

Animals↗