[Importance of the discovery of endorphins and enkephalins for present-day psychopharmacology].
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Animals↗
Biomedical subjects
Z S Herman
Publications and source records attributed to Z S Herman.
Metabolic effects of long-term diversion of renal venous blood into the portal system.
In 7 splenectomized dogs a left renal vein-splenic vein anastomosis was performed and the right kidney removed. Eighteen to twenty-four months after portalization of renal venous blood no significant alterations of liver function tests were observed. Long-term diversion of renal venous blood into the liver was followed by a slight increase of creatinine and 25-OH-D, a decrease of alpha-amino acid nitrogen in blood plasma and of plasma renin activity in peripheral blood, by signs of slight carbohydrate intolerance despite hyperinsulinaemia, and a slight decrease of erythrocyte count. No influence of this procedure on plasma proteins, lipids, electrolytes, aldosterone and cortisol was found. No morphological abnormalities in the liver and kidney tissue were found.
Aldosterone↗
Interaction on the antinociceptive effect between neurotensin and enkephalins or tuftsin.
The aim of this paper was to study the interaction between neurotensin and both enkephalins or its synthetic analogue D-Ala2-metenkephalinamide, or tuftsin, on the antinonciceptive effect of these peptides in mice after intracisternal injection. Antinociception was measured by the hot-plate method. It was shown that neurotensin antagonized evidently the antinociceptive effect of enkephalins and their analogue. On the contrary, neurotensin and tuftsin were agonists in induction of analgesia. It is concluded that neurotensin modulates in an opposite way the function of the enkephalinergic neurons and the central action of tuftsin.
Animals↗
[Chemical agents exerting specific adverse effects on neurons synthesizing biogenic amines].
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Animals↗
Effect of prostaglandins on morphine-induced catalepsy in mice.
The effect of prostaglandins (PGs) F1 alpha, F2 alpha, E1, E2, D2, I2, A1, B1 injected into the lateral ventricle of the brain on morphine-induced catalepsy was studied in mice. The PGs were administered in doses of 1 microgram, the dose of morphine was 30 mg/kg intraperitoneally. It was found that PGs E1, E2 and D2 weakened, and F1 alpha, F2 alpha and I2 increased morphine-induced catalepsy. The results of this experiment showed a modifying effect of exogenous PGs on morphine-induced catalepsy, the effect differed depending on the prostaglandin used.
Animals↗
The diuretic action of noradrenaline and dopamine in rats with chemical serotoninectomy and central nervous system sympathectomy.
It was demonstrated that dopamine administered into the lateral ventricle of rats with chemically induced sympathectomy of the central nervous system had an evident diuretic effect observed 4 as well as 24 hours after its injection. Noradrenaline, on the other hand, increased diuresis in control rats and in those with chemical serotoninectomy, but only in the first 4 hours of the experiment. Chemical sympathectomy of the central nervous system abolished the diuretic effect of noradrenaline. The results of the experiment confirm the role of mainly dopaminergic receptors in the central regulation of diuresis in this experimental model.
5,6-Dihydroxytryptamine↗
The influence of biogenic amines and cyclic nucleotides on rats' bhavior after the chemical serotoninectomy of the central nervous system.
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5,6-Dihydroxytryptamine↗
The concentration of gamma-aminobutyric acid (GABA) in discrete areas of rat brain after chemical sympathectomy or serotoninectomy.
It was shown that central chemical sympathectomy by 6-hydroxydopamine and central chemical serotoninectomy by 5,6-dihydroxytryptamine diminish the level of gamma-aminobutyric acid in discrete areas of rat brain.
5,6-Dihydroxytryptamine↗
Effect of prostaglandin synthesis inhibition on the central activity of noradrenaline in rats.
The effects of paracetamol and indomethacin on the action of centrally administered noradrenaline (NA) on the blood pressure, heart rate and rectal body temperature were studied in rats. It was demonstrated that both these substances increased NA effect on the arterial blood pressure and heart rate but caused no changes in NA effect on body temperature. These results suggest a modulating action of prostaglandins in the central nervous system on the functions of the centres regulating cardiovascular functions.
Acetaminophen↗
Central effects of prostaglandin D2.
In male Wistar rats PGD2 was injected introcerebroventricularly in a dose of 1, 10 or 50 microgram. PGD2 did not produce change in rat behavior and did not change the body temperature, blood pressure and respiration. PGD2 potentiated slightly the catalepsy elicited by chloropromazine or haloperidol, and in high dose had weak cataleptogenic effect. PGD2 changed the level of GABA i some brain areas. In general, however, the central effects of PGD2 are almost negligible.
Animals↗
Effects of intrahypothalamic injections of kainic acid on the behaviour of rats.
The effects of bilateral microinjections of kainic acid 1.0 microgram and 2.5 micrograms into the hypothalamus on the behaviour of rats were studied controlling this behaviour during 2 weeks by the method of Lat. Moreover, the exploratory activity and irritability of the animals were assessed during that time period. After 2 weeks the activity of acetyltransferase and the level of GABA were determined in rat brain. Bilateral injections of kainic acid produced only slight changes in rat behaviour, no changes in the activity of acetyltransferase in the hypothalamus, but raised significantly the level of GABA in this structure and in the thalamus. The results of these investigations point out indirectly that the hypothalamus contains no greater number of cell bodies of cholinergic neurons but it may contain cholinergic and GABA-ergic axons which are not destroyed by kainic acid.
Acetyltransferases↗
Effect of D-Ala2-met-enkephalinamide and morphine on the activity of choline acetyltransferase and acetylcholinesterase in rat brain.
D-Ala2-Met-enkephalinamide injected into the lateral brain ventricle (i.c.v.) in a dose of 100 micrograms increased choline acetyltransferase (AchT) activity in the hypothalamus and thalamus. No changes of AchT activity in the striatum, hippocampus and cortex were found. D-Ala2-Met-enkephalinamide increased also acetylcholinesterase (AchE) activity but only in the hypothalamus. Morphine (10 micrograms i.c.v.) increased AchT activity only in the thalamus. Our results and data from the literature suggest that enkephalins may effect the cholinergic neurons in the brain.
Acetylcholinesterase↗
Effects of clonidine and apomorphine on motor and exploratory activity in mice with frontal lobe lesions.
The reported investigations were carried out on male Porton white mice, which had bilateral lesions of the cortex of frontal lobes made one month before the experiment. In mice with these lesions the excitatory effect of apomorphine (2 mg/kg) and clonidine (0.1 microgram/kg) was abolished, similarly as the inhibitory effect of clonidine (1 mg/kg) on the motor activity. The data indicate that noadrenergic neurons in the frontal lobes participate in the regulation of the motor and exploratory activity in mice.
Animals↗
Pharmacological interaction between neuropeptides and pethidine or fentanyl in rat spinal cord.
Male Wistar rats were treated with pethidine (PT) or fentanyl (FN) subcutaneously (sc) followed by intrathecal (ith) non analgesic doses of methionine- (MENK) or leucine-enkephalin (LENK), neurotensin, (NT), substance P (SP) or cholecystokinin octapeptide 26-33 (CCK-8). Then the antinociceptive effect was measured during 1 h using tail-immersion test. LENK potentiated strongly PT and FN analgesia. MENK antagonized PT analgesia only transiently 30 min after administration and transiently potentiated FN analgesia. SP and CCK-8 potentiated significantly PT analgesia, whereas NT acted biphasically: increasing and then decreasing PT analgesia. SP, CCK-8 and NT augmented FN analgesia. Naloxone inhibited analgesia elicited by the studied opioids and neuropeptides. These data show that LENK affects similarly the analgesic effects of both studied opioids, whereas MENK acted differently on PT and FN analgesia. This may suggest that individual enkephalins have different pharmacological features when interacting with different analgesics. Also NT interacted differently with pethidine and fentanyl.
Analgesics↗
Influence of halothane on the level of enkephalins in discrete brain areas of rabbits.
With regard to the fact, that theory of anesthesia, based on the endogenous opioid peptides requires further investigations the aim of this paper was to measure the concentration of leucine- (LENK) or methionine-enkephalin (MENK) in discrete brain areas of rabbits during and after 1 h halothane (2% v/v) anesthesia. The level of LENK and MENK was measured in discrete brain areas using the radioimmunoassay. Animals were divided into the following groups, depending upon the duration of anesthesia: I-15 min; II-60 min; III-1 h after anesthesia termination; IV-control group of non-anesthetized animals. After halothane anesthesia evident decrease in the concentration of leu-enkephalins in hypothalamus (HT) and the opposite effect in hippocampus (H) were observed. The MENK level significantly increased after halothane (for 60 min) in hypothalamus, hippocampus and mesencephalon (M). The change in the level of LENK in the thalamus (Th), hippocampus and mesencephalon and in the level of MENK in the hypothalamus and mesencephalon persisted after withdrawal of anesthesia. It was found that the alterations in the level of enkephalins in discrete areas of rabbit's brain is a feature of halothane anesthesia. The explanation of this phenomenon is possibly important for the understanding of the mechanism of halothane anesthesia and requires further investigations.
Anesthesia↗
The influence of the kappa agonist-spiradoline (U62066E) on the analgesic activity of some opioids at the spinal level.
Male Wistar rats were treated with morphine (MP) or pentazocine (PT) subcutaneously (sc) and then intrathecally (it) with a specific kappa receptor agonist spiradoline (U62066E). In another series of experiments methionine-(MENK) or leucine-enkephalin (LENK) were injected it with U62066E simultaneously. Then antinociceptive effect on thermal stimulus was measured 1 h using the tail immersion test. MP or LENK induced analgesia was enhanced by U62066E during the first 30 min of observation. MENK analgesic activity was potentiated by kappa receptor agonist only up to 5 min. U62066E acted biphasically on PT antinociceptive effect. These results suggest that kappa opioid receptors may participate in antinociceptive action of MP and LENK and in small degree for analgesic effect of PT and MENK at the spinal level.
Analgesia↗
Influence of ketamine and its interactions with morphine and nalbuphine on the level of enkephalins in some parts of the brain and spinal cord.
The aim of this paper was to study the influence of ketamine in a dose of 80 or 160 mg/kg ip on the level of leu-enkephalin (LENK) or met-enkephalin (MENK) in some parts of the brain and spinal cord, as well as to examine the interaction of ketamine with morphine or nalbuphine on this effect. The influence of ketamine on enkephalins release into the brain perfusate was also studied. Ketamine decreased the spinal cord enkephalins concentration mainly in cervical and lumbar part. These effect was antagonized by naloxone. Ketamine administered in a higher dose increased LENK release, and decreased the release of MENK into the brain perfusate. Morphine (20 mg/kg ip) increased the level of LENK in the hypothalamus, decreased the concentrations of MENK in the medulla oblongata and in the cervical part of the spinal cord, and increased the level of this neuropeptide in the thoracic part of the spinal cord. These effects were antagonized by ketamine. Ketamine and morphine administered simultaneously affected the level of enkephalins in some of the studied parts of the brain and spinal cord. Nalbuphine administered in doses ranging from 1 to 20 mg/kg changed the level of enkephalins in some parts of the central nervous system. Ketamine and nalbuphine administered simultaneously changed the level of enkephalins in the spinal cord and in the hypothalamus. It is concluded that: the decrease of the level of enkephalins in the spinal cord is an evident feature of ketamine action mediated probably by opioid receptors. Ketamine affects the release of LENK and MENK from the brain in a different way.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of Variance↗
Chronic treatment with atypical neuroleptics sulpiride and metoclopramide increases striatal enkephalins in rat brain.
The aim of this paper was to study the effect of a single dose of 14, 30 or 90 days' administration of sulpiride (SUL) (50 or 100 mg/kg), metoclopramide (MET) (20 or 40 mg/kg) or haloperidol (HAL) (2 mg/kg) on the level of leu- and met-enkephalin (ENK) in the striatum. A dose and time dependent increase of the striatal ENK level was observed after chronic administration of atypical neuroleptics SUL or MET as well as after chronic treatment with a classical cataleptogenic neuroleptic HAL. The effect of chronic administration of HAL on the striatal level of leu-enkephalin was stronger than after SUL but lower than after MET treatment. It is concluded that: 1) Chronic administration of atypical neuroleptics results in the increased level of striatal ENK similar to that after chronic treatment with classical cataleptogenic neuroleptics; 2) Apparently both more or less selective antagonists of dopaminergic D2 receptors activate the enkephalinergic system in the striatum.
Animals↗