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Biomedical subjects

G Hertting

Publications and source records attributed to G Hertting.

At least 127 records · Page 7Linked to original sources
PubMed1982

Evidence for inhibition by beta-endorphin of vasopressin release during foot shock-induced stress in the rat.

This study was to ascertain the effect of naloxone and dexamethasone on vasopressin and beta-endorphin release in the rat during inescapable electric foot shock stress. Plasma vasopressin concentrations were not affected by electric foot shock in vehicle-treated rats, but were raised significantly by the stress in animals pretreated with naloxone. The stress-induced increase in plasma beta-endorphin-like immunoreactivity (beta-EI) was similar whether the rats had received naloxone or not. Plasma beta-EI consisted of equal amounts of beta-endorphin-like and beta-lipotropin-like material as revealed by gel filtration. Dexamethasone almost abolished the foot shock-induced increase in plasma beta-EI and, in the presence of dexamethasone, stress was now effective in elevating plasma vasopressin concentrations. These results are consistent with the hypothesis that beta-endorphin, released from the anterior pituitary, inhibits the release of vasopressin from the posterior lobe of the pituitary gland during foot shock-induced stress.

Animals↗
PubMed1981

Formation and elimination of prostacyclin metabolites in the cat in vivo as determined by radioimmunoassay of unextracted plasma.

Using newly develop radioimmunoassay for 6-keto-prostaglandin F1 alpha and 6,15-diketo-13,14-dihydro-prostaglandin F1 alpha, the plasma concentrations of these two prostacyclin derivatives were measured in anaesthetized cats. After the administration of angiotensin II, which releases prostacyclin into the circulation, concentrations of both derivatives rose simultaneously, the major immunoreactivity being 6,15-diketo-13,14-dihydro-prostaglandin F1 alpha. Angiotensin II-induced prostacyclin release was not caused by vasoconstriction alone, since comparable vasopressor responses to noradrenaline and vasopressin were not accompanied by increases in prostacyclin plasma levels. Injection of exogenous prostacyclin resulted in a shortlasting peak of 6-keto-prostaglandin F 1 alpha, which rapidly declined (t 1/2: 1.29-1.52 min). 6,15-diketo-13,14-dihydro-prostaglandin F1 alpha appeared with an t 1/2 of 0.48-1.38 min and was eliminated with a t 1/2 of 8.0-9.0 min. Due to its longer half-life in the circulation 6,15-diketo-13,14-dihydro-prostaglandin F 1 alpha again was the predominant derivative after 3 min. These data suggest that in vivo prostacyclin is mainly inactivated by the 15-hydroxy-PG-dehydrogenase-, delta 13-reductase-pathway, rather than by hydrolysis. Therefore, 6,15-diketo-13,14-dihydro-prostaglandin F1 alpha seems to be a better indicator of prostacyclin plasma levels than 6-keto-prostaglandin F1 alpha, although under certain conditions the additional determinations of this product of hydrolysis can be valuable.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Endogenously formed PGE2 mediates the increase in cAMP accumulation in rabbit splenic fibroblasts following alpha-receptor stimulation.

Prostaglandin E2 synthesis in rabbit splenic fibroblasts was stimulated by noradrenaline but not by isoprenaline. Noradrenaline, isoprenaline and prostaglandin E2 increased intracellular cAMP accumulation. Noradrenaline-, but not isoprenaline-evoked cAMP accumulation was reduced by indomethacin; only combinations of phentolamine or indomethacin with propranolol abolished the noradrenaline effect. We conclude that the noradrenaline-induced increase in cAMP levels of rabbit splenic fibroblasts was due to stimulation of both alpha- and beta-adrenoceptors. The response to alpha-receptor stimulation was possibly mediated by prostaglandin E2.

Animals↗
PubMed1981

Effect of prostaglandins D2, E2 and F2alpha on catecholamine release from slices of rat and rabbit brain.

Slices of rabbit or rat brain cortex were preincubated with [3H]noradrenaline, and slices of rabbit caudate nucleus or rat stratum with [3H]dopamine. The slices were then superfused and stimulated electrically. In rat cortex slices, PGE2 (0.01-1 millimicronmol/l) markedly reduced the stimulation-evoked overflow of tritium. PGF2alpha (1 millimicronmol/l) caused a slight decrease only after the formation of endogenous prostaglandins had been blocked by indomethacin. PGD2 (1 millimicronmol/l) had no effect. In slices of rabbit cortex and caudate nucleus as well as in rat striatal slices, none of the prostaglandins (1 millimicronmol/l) caused any change, irrespective of whether the production of endogenous prostaglandins was intact or blocked. The results show that, of three major prostaglandins that occur in the brain, only PGE2 is a potent presynaptic inhibitor of noradrenaline release in the rat. The catecholamine neurones of rabbit brain, and the dopamine neurones of rat striatum, are resistant to these prostaglandins.

Animals↗
PubMed1981

Lowering of the convulsive threshold by non-steroidal anti-inflammatory drugs.

Administration of convulsant doses of pentetrazole induced an increase of PGF2 alpha, PGE2 and TXB2 immuno-reactive material in mouse brain in vivo. The non-steroidal anti-inflammatory drugs indomethacin, flurbiprofen and diclofenac in equipotent doses inhibited the convulsion-induced increase of prostaglandins and thromboxane B2 (P less than 0.01). The same drugs also lowered the LD50 of pentetrazole (P less than 0.05) and accelerated the onset of tonic seizures evoked by pentetrazole (P less than 0.05). Ibuprofen in a submaximal centrally effective dose acted in the same way on cerebral PG and TXB2 synthesis and on the LD50 of pentetrazole but failed to influence significantly the latency time to the onset of pentetrazole-induced tonic seizures. Aspirin (100 mg/kg) and paracetamol (30 mg/kg), which were without effect on cerebral PG and TXB2 concentrations following pentetrazole-induced seizures, were also ineffective in lowering the convulsive threshold and the LD50 of pentetrazole. It is concluded that non-steroidal anti-inflammatory drugs act on the convulsive threshold by inhibition of cerebral prostaglandin and/or thromboxane synthesis.

Animals↗
PubMed1981

The effect of isoprenaline on plasma concentrations of immunoreactive beta-endorphin and beta-lipotropin in the conscious rat.

The effect of the beta-adrenoceptor agonist isoprenaline on the plasma concentrations of beta-endorphin (beta-E) and beta-lipotropin (beta-LPH) was investigated in conscious rats. Isoprenaline (i.m.) elevated plasma beta-endorphin-like immunoreactivity (beta-EI) as measured by radioimmunoassay of unextracted plasma, with peak values 24 min after drug administration. This effect was dose-dependent. The lowest effective dose of isoprenaline was 15 micrograms kg-1; 240 micrograms kg-1 exerted a maximum effect, raising plasma beta-EI about ten-fold above control values. Plasma vasopressin concentrations also increased in response to isoprenaline following a time-course identical to that of plasma beta-EI. (+/-)-Propranolol (1 mg kg-1) but not phentolamine (10 mg kg-1) rendered isoprenaline (240 micrograms kg-1) injections almost ineffective. Because of the cross-reactivity of beta-LPH in the radioimmunoassay used, plasma was extracted by means of a cation exchange resin and subjected to gel chromatography on a Sephadex G-50 column, avoiding artefactual degradation of the peptides. In isoprenaline-treated rats about 50% of the beta-EI behaved similar to human beta-LPH, whereas 45% co-migrated with human beta-E; immunoreactivity corresponding to beta-LPH or beta-E comprised about 70% or 30%, respectively, in the plasma extract of vehicle-treated rats. Dexamethasone pretreatment reduced the isoprenaline-induced increase in plasma beta-EI by 87%, but left the simultaneous elevation of plasma vasopressin concentrations unchanged. These data demonstrate that isoprenaline stimulates beta-LPH and beta-E release in vivo. The possibility of an interrelationship between vasopressin and beta-E release is discussed.

Animals↗
PubMed1981

Stimulation of prostaglandin E2-synthesis by noradrenaline in primary cell cultures from rabbit splenic pulpa is mediated by atypical alpha-adrenoceptors.

In primary cell cultures originating from rabbit splenic pulpa the effects of various adrenoceptor agonists on prostaglandin (PG)-synthesis were studied. The cells - microscopically identified as fibroblasts - released PGs into the medium: especially PGE2 besides small amounts of PGF2alpha and PGD2. Noradrenaline increased dose-dependently the amount of PGs released into the medium. Besides noradrenaline, only the catecholamines adrenaline and alpha-methylnoradrenaline strongly activated PG-synthesis. Other alpha-adrenoceptor agonists like the phenylethylamine and imidazoline derivatives were only weak agonists or completely ineffective. All adrenoceptor agonists without intrinsic activity in these cells antagonized the noradrenaline effect on PG-synthesis, the imidazolines being more potent antagonists than the phenylethylamines. The beta-adrenoceptor agonist isoprenaline stimulated PG-synthesis at high concentration only. The effects of both noradrenaline and isoprenaline were inhibited by low concentrations of phentolamine phenoxybenzamine, but not by propranolol. The preferential alpha2-adrenoceptor antagonists yohimbine and rauwolscine were about 50 times more potent in blocking the noradrenaline effect on PG-synthesis than the more alpha1-specific antagonist corynanthine. However, prazosin, another alpha1-adrenoceptor antagonist, was about equipotent with yohimbine. It is concluded that noradrenaline elicits PG-synthesis in rabbit splenic fibroblasts via alpha-adrenoceptor stimulation. The alpha-adrenoceptor involved has properties which are different from those reported so far for alpha1- or alpha2-adrenoceptors.

Animals↗
PubMed1981

Vasopressin stimulates release of beta-lipotropin and beta-endorphin in conscious rats as measured by radioimmunoassay of unextracted plasma.

Using a newly developed radioimmunoassay to determine the beta-endorphin-like immunoreactivity (beta-EI) in unextracted plasma, the effect of vasopressin injections on plasma beta-EI was investigated in conscious rats. Arginine vasopressin caused a dose-dependent increase of plasma beta-EI from 34.5 to 7.8 fmol ml--1 (n = 6) in vehicle-treated animals to 205.0 +/- 36.1 fmol ml--1 (n = 7) after injection of the highest vasopressin dose employed (486 ng/100 g b.w.). In view of the appreciable cross-reactivity of beta-lipotropin (beta-LPH) in the radioimmunoassay used, plasma was extracted and subjected to gel chromatography on a Sephadex G-50 column. On average, about 70% of the beta-EI co-eluted with human beta-LPH and about 30% with human beta-endorphin in plasma extracts obtained from both control and vasopressin-treated rats. No peripheral conversion of human beta-LPH occurred under the experimental conditions, since after i.v. bolus injection of human beta-LPH 97% of the beta-EI comigrated with human beta-LPH during gel filtration. A similar blood pressure increase to that induced by the vasopressin injections, when elicited by noradrenaline or angiotensin II i.v., was not followed by an elevation of plasma beta-EI. These data indicate that vasopressin stimulates beta-lipotropin and beta-endorphin release into the systemic circulation in vivo.

Animals↗
PubMed1981

Regional distribution of arachidonic acid metabolites in rat brain following convulsive stimuli.

Seizures were induced in female Wistar rats by electroconvulsive shock (ECS) or administration of pentetrazole (PTZ). Brain content of various prostanoids measured by radioimmunoassay showed time-dependent changes after the induction of convulsions; highest levels were found for PGD2 followed by PGF2 alpha, PGE2, TXB2 and 6-keto-PGF1 alpha. Analysis of the various arachidonic acid metabolites in seven parts of the rat brain dissected according to the method of Glowinski and Iversen revealed the largest increases in hippocampus and cerebral cortex and smaller ones also in hypothalamus and corpus striatum both after ECS and PTZ. The ratios of the different cyclo-oxygenase products remained virtually the same in whole brain as well as in those regions where the formation of prostaglandins was markedly elevated. 15-keto-13,14-dihydro-PGF2 alpha also increased simultaneously in parallel to its parent compound, PGF2 alpha and was detected in significant amounts only in hippocampus and cerebral cortex. However, concentrations of 15-keto-13,14-dihydro-PGF2 alpha in these brain regions as well as in whole brain represented only 3-10% of the amounts found for PGF2 alpha. Thus, the metabolizing enzymes 15-hydroxy-PG-dehydrogenase and delta 13-PG-reductase seem to be of minor importance for the inactivation of prostanoids in brain tissue.

Animals↗
PubMed1981

On the mechanism of noradrenaline-induced prostaglandin E2-Synthesis in primary cell cultures from rabbit splenic pulpa.

The role of Ca2+ and phospholipase A2 in alpha-adrenoceptor mediated stimulation of prostaglandin (PG)E2-release was investigated in primary cell cultures of rabbit splenic pulpa. Noradrenaline enhanced PGE2-release only in the presence of extracellular Ca2+. In contrast, PGE2-release induced by arachidonic acid was unchanged when Ca2+ was omitted. In the presence of Ca2+, the ionophore A 23187 increased PGE2-release concentration-dependently. During incubation in Ca2+-free medium, the ionophore was ineffective. Inhibitors of phospholipase A2 (mepacrine, p-bromophenacyl bromide) abolished the noradrenaline-induced PGE2-release and reduced the effect of A 23187; the stimulation of PGE2-release by arachidonic acid was not affected. Addition of exogenous phospholipase A2 enhances release of PGE2. From these results we suggest that noradrenaline-induced PGE2-release in rabbit splenic fibroblasts via alpha-adrenoceptors involves the following steps: influx of Ca2+, activation of a Ca2+-dependent phospholipase and liberation of arachidonic acid which is transformed into PGs.

Animals↗
PubMed1980

Evidence that vasopressin is involved in the isoprenaline-induced beta-endorphin release.

We investigated in conscious rats, whether vasopressin, whose release was stimulated by isoprenaline (i.m.), caused the simultaneous increase in plasma beta-endorphin-like immunoreactivity (beta-EI). The increase in plasma beta-EI following isoprenaline administration was diminished by about 50% in rats pretreated with a vasopressin antagonist and also in rats with a hereditary absolute lack of vasopressin. We conclude that the isoprenaline-induced release of beta-EI is mediated in part by vasopressin.

Animals↗
PubMed1980

On the relation between contraction and prostaglandin release in rabbit mesenteric blood vessels.

The rabbit superior mesenteric artery and portal vein were used for a study of the effects of noradrenaline, high potassium, angiotensin II and bradykinin on both the contraction development and PG synthesis (PGE2 and PGF2 alpha) in tissue. Noradrenaline induced contractions but no PG release, high potassium evoked contractions and PG release, angiotensin II elicited contractions and PG release in the mesenteric artery but only PG release in the portal vein, and bradykinin initiated PG release and a small decrease in basal tone. The stimulus-evoked PG release was Ca2+-dependent. It is concluded that, at least in some tissues, stimulus-evoked PG release is completely independent from the contractile mechanism. The variable pattern in contractile responses and stimulus-evoked PG release in various tissue may depend on variations of the stimulus-induced accessibility of Ca2+ ions to either phospholipase A2 or the contractile apparatus.

Angiotensin II↗
PubMed1980

Modulation by endogenous dopamine of the release of acetylcholine in the caudate nucleus of the rabbit.

Slices of the caudate nucleus of rabbits were preincubated with 3H-choline and then superfused. Stimulation by electrical pulses at 3 Hz or by 25 mmol/l potassium elicited an increase in tritium outflow which was calcium-dependent and, in the case of electrical stimulation, tetrodotoxin-sensitive. The dopamine receptor agonist apomorphine (0.01-1 mumol/l) decreased, whereas the antagonist haloperidol increased the electrically evoked overflow of tritium. Nomifensine and cocaine, used at concentrations known to inhibit the re-uptake of dopamine, also reduced the evoked overflow of tritium, and this reduction was antagonized by haloperidol. Combined pretreatment with reserpine and alpha-methyltyrosine methylester (alpha-MT), which lowered dopamine levels by 99.5%, increased the electrically evoked overflow, as did bretylium which is shown here to block action potential-induced release of dopamine. The facilitation by haloperidol and bretylium as well as the inhibition by nomifensine and cocaine were diminished or abolished after pretreatment with reserpine plus alpha-MT. Apomorphine decreased, and haloperidol increased, the potassium-evoked overflow of tritium; the effects were not changed by tetrodotoxin. The results indicate that the striatal dopamine receptors which, when activated, depress the release of acetylcholine, are akin to the D-2 type. Endogenous dopamine also acts on the receptors as shown by several manipulations with known effects on dopaminergic transmission. A large fraction of these dopamine receptors may be located on the cholinergic axon terminals.

Acetylcholine↗
PubMed1980

Interneurones are probably not involved in the presynaptic dopaminergic control of dopamine release in rabbit caudate nucleus.

Slices of rabbit caudate nucleus were preincubated with 3H-dopamine and then superfused. The influence of apomorphine and haloperidol on the overflow of tritium evoked by 20 mmol/l potassium was investigated in the presence and in the absence of tetrodotoxin. The potassium-evoked overflow was largely calcium-dependent and consisted mainly of 3H-dopamine. The dopamine receptor agonist apomorphine 0.01-1.0 mumol/l reduced, whereas the antagonist haloperidol 0.1 mumol/l enhanced the potassium-evoked overflow of tritium. The effects of apomorphine and haloperidol were as pronounced in the presence as in the absence of tetrodotoxin 0.3 mumol/l. It is concluded that the presynaptic dopaminergic modulation of dopamine release is not mediated by a tetrodotoxin-sensitive interneuronal pathway.

Action Potentials↗
PubMed1980

Evidence for the involvement of a GABA-mediated inhibition in the hypovolaemia-induced vasopressin release.

The influence of GABA and of drugs, known to alter GABA-metabolism, on the hypovolaemia-provoked vasopressin release was investigated in rats. Blood volume was decreased without altering plasma osmolality or arterial blood pressure by i.p. injection of polyethylene glycol and the resulting plasma vasopressin concentration was measured using a radioimmunoassay. I.c.v. injections of GABA (0.4-2 mg) markedly suppressed the hypovolaemia-induced vasopressin release. The central inhibitory effect of GABA could not be related to appropriate changes in peripheral parameters believed to regulate vasopressin release (arterial blood pressure, renin-angiotensin system). Aminooxyacetic acid (9-81 mg kg-1, i.m.) and gamma-vinyl-GABA (1.5 g kg-1, i.p.), two potent inhibitors of GABA aminotransferase and known to increase brain GABA content, reduced vasopressin release to a comparable degree as did GABA (i.c.v.). On the other hand, 3-mercaptopropionic acid (10-90 mg kg-1, i.p.), an inhibitor of the GABA synthetizing enzyme glutamic acid decarboxylase, promoted the release of vasopressin when the rats were killed prior to the onset of convulsions. These results, on the whole, intimate the existence of a GABA-mediated inhibition in the central control of vasopressin release.

3-Mercaptopropionic Acid↗
PubMed1979

[The sympathetic neuron: regulation mechanisms for transmitter synthesis, transmitter release, and stimulus response (author's transl)].

A great multitude of factors acting at different sites of the afferent sympathetic nerve are capable to modify the magnitude of its stimulus-induced effects. 1) Specific receptors, located at the ganglionic synapse display inhibitory of facilitatory effects on the ganglionic transmission of the nerve impulse. 2) The rate of synthesis of the neurotransmitter noradrenalin is regulated at the level of the tyrosine hydroxylase. Transsynaptic mechanisms adapt the rate of synthesis of noradrenalin to nerve activity and transmitter release. 3) The amount of transmitter released per nerve impulse is controlled by a variety of receptors located presumably presynaptically at neuronal sites. Inhibitory and facilitatory "auto"-receptors stimulated by the released transmitter itself represent a local feed-back control. Similarly receptors for transmitters of cholinergic or serotoninergic neurons as well as autacoid hormones are involved in the local control of noradrenalin release. In addition, kinines, prostaglandins, or compounds like adenosine, some of them released from the target cells by the sympathetic stimuli or delivered by the blood stream are involved in the modulation of stimulus-evoked noradrenalin release. 4) Stimulus responses of the target cells can be modulated by similar mechanisms.

Humans↗