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Biomedical subjects

G Hertting

Publications and source records attributed to G Hertting.

At least 91 records · Page 5Linked to original sources
PubMed1986

Serotonin (5-HT) enhances hippocampal noradrenaline (NA) release: evidence for facilitatory 5-HT receptors within the CNS.

Slices of rabbit hippocampus were preincubated with 3H-noradrenaline (3H-NA), then superfused continuously in the presence of the noradrenaline (NA) uptake inhibitor (+)oxaprotilin and twice stimulated electrically. The stimulation induced tritium overflow was increased by the 5-HT receptor agonists, 5-HT, 2-methyl-5-HT and 5-carboxamidotryptamine in a concentration dependent manner; a tyramine-like displacement of NA by the 5-HT agonists was prevented by (+)oxaprotilin. The 5-HT M-receptor antagonists, MDL 72222 and ICS 205-930, inhibited the facilitatory effects of 5-HT agonists as well as the enhanced tritium overflow due to the selective 5-HT uptake inhibitor, 6-nitroquipazine: in each case, concentrations much higher than those required to block M-receptors of the periphery were necessary. At high concentrations MDL 72222, in contrast to ICS 205-930, seems to have alpha-adrenoceptor antagonistic activity. The 5-HT2 receptor antagonist, ketanserin, had no effect on 5-HT-induced facilitation of transmitter release; metitepin facilitated stimulation-evoked transmitter release per se both in the absence and presence of phentolamine. From our results we conclude that, as on peripheral nerve endings, also on central noradrenergic terminals, facilitatory 5-HT receptors are present that modulate NA release. The enhanced tritium overflow following 6-nitroquipazine may be due to an increased release of endogenous 5-HT, a suggestion which supports the hypothesis of a physiological innervation of these facilitatory 5-HT receptors on NA terminals.

Animals↗
PubMed1986

The possible involvement of cytochrome P-450 monooxygenase in AVP-induced ACTH secretion.

AVP (10(-7) M) induced ACTH as well as PGE2 release from rat anterior pituitary quarters. Inhibitors of P-450 monooxygenase, metyrapone (10 mM) and piperonyl butoxide (1 mM and 10 mM) attenuated the ACTH and PGE2 response to AVP. 7,8-benzoflavon (10 mM) which inhibits 3-methylchloranthrene inducible form of P-450 isoenzymes showed no inhibition of AVP-induced ACTH secretion. The decrease in ACTH response to AVP was still observed following the inhibition of prostaglandin synthesis by indomethacin. These results suggest that cytochrome P-450 monoocygenase systems are involved in the process of AVP-induced ACTH secretion, 3-methylchloranthrene inducible form of P-450 isoenzymes do not seem to be involved in this process.

Adrenocorticotropic Hormone↗
PubMed1986

Delta-sleep-inducing peptide (DSIP) inhibited CRF-induced ACTH secretion from rat anterior pituitary gland in vitro.

Delta-sleep-inducing peptide (DSIP, 10(-9) - 10(-7) M) significantly inhibited the CRF-induced ACTH release from rat anterior pituitary quarters in vitro. 10(-8) M DSIP showed the most prominent inhibition. DSIP (10(-8) M) also inhibited the CRF-activated cAMP levels in anterior pituitary tissue. DSIP did not influence basal ACTH or cAMP levels. Prostaglandin E2 (PGE2)-release from anterior pituitary quarters was not changed by DSIP. From these results, we conclude that DSIP inhibits CRF-induced ACTH release at the pituitary level through the inhibition of the cAMP system in corticotrophs. The involvement of PGE2 in this phenomenon is unlikely.

Adrenocorticotropic Hormone↗
PubMed1986

The role of endothelial and non-endothelial prostaglandins in the relaxation of isolated blood vessels of the rabbit induced by acetylcholine and bradykinin.

Strips of rabbit extrapulmonary, coeliac and mesenteric arteries were mounted in organ baths for isotonic recording of changes in tissue length. The formation by the strips of the vasodilator prostaglandins PGI2 (measured as 6-keto-PGF1 alpha) and PGE2 was determined by specific radioimmunoassays. Removal of vascular endothelium initially increased and then permanently decreased the basal prostaglandin release of the tissues. Acetylcholine (ACh) relaxed strips of all three arteries if the endothelium was intact. ACh also stimulated the formation of PGI2 and PGE2 from all three tissues; about 60% of these prostaglandins originated from endothelial cells. Indomethacin caused complete inhibition of prostaglandins formation and a slight inhibition of the ACh-relaxation (not statistically significant). Complete inhibition of the ACh relaxation was achieved with nordihydroguaiaretic acid (NDGA). NDGA also partially inhibited prostaglandin formation. These data suggest that in blood vessels that are also prostaglandin-sensitive, the ACh relaxation is predominantly mediated by a non-prostaglandin endothelium-derived relaxing factor. Bradykinin was more potent that ACh in releasing prostaglandins from the same arteries. This release was activated in subendothelial components of the vascular wall. Neither this prostaglandin release nor the bradykinin-induced relaxations were significantly reduced in endothelium-denuded arteries. Indomethacin completely blocked the bradykinin-induced prostaglandin release and the bradykinin relaxation. NDGA caused a moderate inhibition of the bradykinin-induced prostaglandin release and slightly attenuated the bradykinin relaxation (neither effect of NDGA was statistically significant). Under all experimental conditions (control, indomethacin, NDGA) and with all three arteries there was a good correlation between the bradykinin-induced prostaglandin release and the respective mechanical response. No such correlation could be found for ACh. Prostaglandin-dependent relaxations of the coeliac and mesenteric artery are probably mediated by endogenous PGI2. The extrapulmonary artery is rather insensitive to PGI2 and is probably relaxed mainly by endogenous PGE2.

Acetylcholine↗
PubMed1986

False labelling of dopaminergic terminals in the rabbit caudate nucleus: uptake and release of [3H]-5-hydroxytryptamine.

The effect of the catecholamine uptake inhibitor nomifensine and of the 5-hydroxytryptamine (5-HT) uptake blocker 6-nitroquipazine on the accumulation of [3H]-5-HT (0.1 microM, 60 min incubation) and [3H]-dopamine (0.1 microM, 30 min incubation) into slices of hippocampus and caudate nucleus of the rabbit was investigated. In addition, the influence of nomifensine on the electrically evoked [3H]-5-HT release from caudate nucleus slices and of nomifensine and 6-nitroquipazine on [3H]-5-HT released from caudate nucleus slices was analysed. In hippocampal slices, which contain practically no dopaminergic but densely distributed 5-hydroxytryptaminergic and noradrenergic nerve terminals (ratio of dopamine:5-HT:noradrenaline about 1:30:25), nomifensine (1, 10 microM) did not affect the accumulation of [3H]-5-HT; 6-nitroquipazine (1 microM) reduced [3H]-5-HT uptake to about 35% of controls. In the caudate nucleus, however, where dopamine is the predominant monoamine (ratio of dopamine:5-HT:noradrenaline about 400:25:15) nomifensine (1, 10 microM) reduced the tritium accumulation to 65% whereas 6-nitroquipazine (1 microM) was ineffective. The combination of both drugs (1 microM each) led to a further decrease to about 15%. The uptake of [3H]-dopamine into hippocampal slices was blocked by both nomifensine (1 microM) and 6-nitroquipazine (1 microM) whereas in caudate nucleus slices only nomifensine (1, 10 microM) reduced the accumulation of [3H]-dopamine. The combination of both drugs was not more effective than nomifensine alone. The different effects of both uptake inhibitors in the hippocampus and caudate nucleus suggest a neurone specific rather than a substrate specific mode of action. 4 In caudate nucleus slices incubated with [3H]-5-HT and superfused continuously the electrically evoked 5-HT release was diminished by the D2-dopamine receptor agonist LY 171555 and enhanced by the D2-receptor antagonist domperidone. If, however, the labelling of caudate nucleus slices was performed in the presence of I microM or 1O microM nomifensine, the modulation of 5-HT release via D2- receptors was reduced or abolished, respectively. In the hippocampus both LY 171555 and domperidone were completely ineffective in modulating 5-HT release regardless of the absence or presence of nomifensine. 5 The present results indicate that an inverse cross labelling of [3H]-5-HT into dopaminergic and of [3H]-dopamine into 5-hydroxytryptaminergic terminals may occur despite the low concentration (0.1 microM) oftritiated transmitters used. Such cross labelling, as demonstrated with the incubation period of 60 min in the caudate nucleus, may falsely indicate the existence of D2-dopamine receptors modulating [3H]-5-HT release. If both 5-hydroxytryptaminergic and dopaminergic terminals are present within the brain region under investigation false labelling can be corrected using neuronally specific uptake inhibitors.

Animals↗
PubMed1986

Bradykinin-induced ACTH release from rat pituitary tissue in vitro.

Bradykinin (10(-6) and 10(-5) M) stimulated ACTH-IR release from rat anterior pituitary tissue in vitro concentration-dependently. The onset of this effect was delayed in comparison to that of AVP or CRF. The combined treatment of bradykinin with AVP or CRF produced additive effects of ACTH-IR release. Bradykinin may represent another candidate involved in the regulation of ACTH release. In contrast to AVP, bradykinin did not stimulate prostaglandin E2 synthesis in the pituitary tissue. Bradykinin-induced ACTH-IR release remained unchanged following cyclooxygenase inhibition by indomethacin. It can be concluded that prostaglandins are not involved in the action of bradykinin on the anterior pituitary. Bradykinin did stimulate cyclic AMP accumulation in pituitary tissue. Inhibition of phosphodiesterase by 3-isobutyl-l-methylxanthine (IBMX) potentiated the ACTH-IR release evoked by bradykinin. From the results obtained, we concluded that cyclic AMP appears to be involved as a second messenger in the bradykinin-evoked ACTH-IR release.

1-Methyl-3-isobutylxanthine↗
PubMed1985

The formation and regional distribution of prostaglandins D2 and F2 alpha in the brain of spontaneously convulsing gerbils.

The distribution of the two major cyclooxygenase products prostaglandin D2 (PGD2) and prostaglandin F2 alpha (PGF2 alpha) in 7 different regions of the brain (medulla, cerebellum, hypothalamus, striatum, midbrain, hippocampus and cerebral cortex) was studied. Basal levels were highest in hypothalamus and cortex. Following convulsions elicited by environmental stress prostaglandin concentrations increased in all areas, with largest increases (10-20-fold) in hippocampus and cortex, reaching 70 ng/g PGD2 in hippocampus and 115 ng/g PGD2 in cortex. These results demonstrate that, during spontaneous seizures, there is a greater increase in prostanoid production in those areas involved in the convulsive process.

Animals↗
PubMed1985

Modulation of hippocampal serotonin (5-HT) release by endogenous adenosine.

Slices of rabbit hippocampus were preincubated with [3H]serotonin then superfused continuously and stimulated twice electrically. The stimulation-evoked overflow of tritium was Ca2+-dependent, tetrodotoxin-sensitive and subject to modulation by serotonin autoreceptors. It was decreased by various adenosine receptor agonists in an order of potency that was typical for A1-(Ri-) receptors: N6-cyclohexyladenosine greater than (-)N6-phenylisopropyladenosine greater than 5'-N-ethylcarboxamideadenosine greater than (+)N6-phenylisopropyladenosine = adenosine. The effects of the agonists were antagonized by 8-phenyltheophylline. The hypothesis that endogenous adenosine influences hippocampal serotonin release is supported by the following findings: both the adenosine receptor antagonists (theophylline or 8-phenyltheophylline (10 microM, each)) and the enzyme adenosine deaminase (10 micrograms/ml) increased, whereas R-E 244 (3 microM), an inhibitor of adenosine uptake, significantly decreased the evoked tritium overflow. When 8-phenyltheophylline was present throughout superfusion the effects of both R-E 244 and exogenous adenosine deaminase were abolished. It is concluded that serotonin release in the rabbit hippocampus is depressed by endogenous adenosine via A1-(Ri-) receptors.

Adenosine↗
PubMed1985

Dopaminergic modulation of hippocampal noradrenaline release. Evidence for alpha 2-antagonistic effects of some dopamine receptor agonists and antagonists.

3H-Noradrenaline release in the rabbit hippocampus and its possible modulation via presynaptic dopamine receptors was studied. Hippocampal slices were preincubated with 3H-noradrenaline, continuously superfused in the presence of cocaine (30 mumol/l) and subjected to electrical field stimulation. The electrically evoked tritium overflow from the slices was reduced by 0.1 and 1 mumol/l dopamine and apomorphine, but significantly enhanced by 10 mumol/l apomorphine or by 0.1 and 1 mumol/l bromocriptine. If the alpha 2-adrenoceptor antagonist yohimbine (0.1 mumol/l) was present throughout superfusion, the inhibitory effects of dopamine and apomorphine were more pronounced and even 10 mumol/l apomorphine and 1 mumol/l bromocriptine inhibited noradrenaline release. Qualitatively similar observations were made in the presence of another alpha 2-antagonist, idazoxane (0.1 mumol/l). In the presence of the D2-receptor antagonist domperidone (0.1 mumol/l) the inhibitory effects of dopamine were almost abolished, whereas both apomorphine (greater than 1 mumol/l) and bromocriptine (greater than 0.01 mumol/l) greatly facilitated noradrenaline release. The D2-receptor agonist LY 171555 (0.1 and 1 mumol/l) significantly reduced the evoked noradrenaline release whereas the D1-selective agonist SK & F 38393 was ineffective at similar concentrations. The effects of LY 171555 were abolished in the presence of domperidone (0.1 mumol/l) but remained unchanged in the presence of yohimbine or idazoxane (0.1 mumol/l, each). At 1 mumol/l the D2-receptor antagonists domperidone and (-)sulpiride significantly increased the evoked noradrenaline release by about 10%. However, at this concentration, domperidone (but not (-)sulpiride) affected also basal tritium outflow. Bulbocapnine and the preferential D1-receptor antagonists SCH 23390 enhanced the evoked noradrenaline release already at 0.1 mumol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1985

Endogenous noradrenaline as modulator of hippocampal serotonin (5-HT)-release. Dual effects of yohimbine, rauwolscine and corynanthine as alpha-adrenoceptor antagonists and 5-HT-receptor agonists.

The modulation of hippocampal serotonin (5-HT)-release by noradrenaline was studied in rabbit hippocampal slices, which were preincubated with 3H-serotonin and then superfused continuously. Electrical field stimulation of the slices elicited a tritium overflow, which was decreased by clonidine in a concentration dependent manner. Phentolamine antagonized the effects of clonidine and, given alone, increased the evoked tritium overflow. This facilitatory effect of phentolamine was further enhanced in the presence of (+)oxaprotilin, a highly selective noradrenaline uptake inhibitor, whereas the (-)enantiomer of oxaprotilin, which does not affect noradrenaline uptake, was inactive. (+)Oxaprotilin but not (-)oxaprotilin, given alone, inhibited the evoked tritium overflow. The inhibitory effect of (+)oxaprotilin was antagonized by phentolamine. In the presence of phentolamine, the alpha-adrenoceptor antagonists yohimbine, rauwolscine and corynanthine decreased the evoked 5-HT-release concentration dependently. Their inhibitory effects were, however, abolished (corynanthine) or inversed to a facilitation of release (yohimbine, rauwolscine) if instead of phentolamine the 5-HT-receptor antagonist metitepin was present. Therefore we suggest that yohimbine, rauwolscine and corynanthine, in addition to their alpha-adrenoceptor antagonistic properties, may act as agonists at 5-HT-autoreceptors. Possibly the indol part of their molecules is responsible for this effect. Furthermore, our results provide evidence for the modulation of hippocampal 5-HT-release by endogenous noradrenaline.

Animals↗
PubMed1985

Islet-activating protein (pertussis toxin) diminishes alpha 2-adrenoceptor mediated effects on noradrenaline release.

The effect of islet-activating protein (IAP) on alpha 2-adrenoceptor mediated modulation of noradrenaline release in the rabbit hippocampus was studied. Slices of the hippocampus were incubated for 6 h with IAP, subsequently loaded with 3H-noradrenaline and superfused continuously. IAP-pretreatment significantly enhanced the electrically evoked transmitter release and diminished the facilitatory effect of the alpha 2-adrenoceptor antagonist yohimbine. In addition, the inhibitory effect of the alpha 2-adrenoceptor agonist clonidine was reduced. These results provide circumstantial evidence that an inhibitory guanine-nucleotide-binding protein, most probably Ni of a presynaptically located adenylate cyclase, is involved in the alpha 2-autoreceptor mediated modulation of noradrenaline release.

Adenylate Cyclase Toxin↗
PubMed1985

Adenosine: an endogenous modulator of hippocampal noradrenaline release.

In slices of hippocampus from the rabbit, preincubated with [3H]noradrenaline and then continuously superfused, the modulation of the release of noradrenaline by adenosine receptors was studied. Electrical field stimulation of the slices elicited a release of [3H]noradrenaline which was inhibited in a concentration-dependent manner by various adenosine receptor agonists. From the order of potency: cyclohexyladenosine greater than (-)phenylisopropyladenosine [(-)PIA] greater than 5'-N-ethylcarboxamide-adenosine (NECA) greater than 2-chloro-adenosine greater than adenosine (+)phenylisopropyladenosine greater than ATP, the inhibitory adenosine receptor was classified as A1- (Ri-) receptor. The effect of the agonist was strongly reduced by adenosine receptor antagonists, the methylxanthines. A role for endogenous adenosine in the modulation of hippocampal noradrenaline release is supported by these findings: (1) that blockade of adenosine receptors by methylxanthines, especially by 8-phenyltheophylline, increased, whereas (2) inhibition of the uptake of adenosine decreased the evoked release of noradrenaline and (3) that deamination of endogenous extracellular adenosine by addition of adenosine deaminase to the medium enhanced the evoked transmitter release. Inhibitors of endogenous adenosine deaminase and 5'-nucleotidase were without effect. It is concluded that release of noradrenaline in the hippocampus is inhibited at the level of the noradrenergic nerve terminals by endogenous adenosine via A1 (or Ri) receptors.

Adenosine↗
PubMed1985

Studies on the mechanism of central cardiovascular and temperature responses to prostaglandin D2.

Administration of prostaglandin D2 (PGD2) into the left lateral cerebral ventricle (i.c.v.) of urethane anaesthetized rats caused increases in blood pressure, heart rate and body temperature. Pretreatment of the animals with the alpha-receptor blocking drug prazosin completely prevented the PGD2-induced rise in blood pressure, but did not affect the chronotropic and hyperpyrexic effects of PGD2. Pretreatment of the rats with the beta-receptor blocking drug propranolol completely suppressed the increase in heart rate, augmented the rise in blood pressure, but reduced the temperature increase by more than 50%. These data indicate that central activation of the sympathetic nervous system mediates the cardiovascular and important parts of the temperature effects of i.c.v.-injected PGD2. The peripheral vasoconstriction (due to the stimulation of sympathetic alpha-receptors) causing the blood pressure increase is obviously of minor importance for the rise in body temperature. In contrast the enhanced production of heat by several organs following beta-receptor activation seems to be an important factor for the temperature increase.

Animals↗
PubMed1985

Radioligand binding studies with 3-(4-(2-hydroxy-3-((1, 1-dimethylethyl)-amino)-propoxy)-phenyl)-7-methoxy-2-methyl- 1(2H)-isoquinolinone (HI-42), a new cardioselective beta-adrenoceptor blocker with long-lasting effects in vivo.

The effects of 3-(4-(2-hydroxy-3-((1, 1-dimethylethyl)-amino)-propoxy)-phenyl)-7-methoxy-2-methyl-1 (2H)-isoquinolinone (HI-42), a cardioselective beta-adrenoceptor antagonist with a long duration of action in vivo, on 3H-dihydroalprenolol (3H-DHA) binding of partially purified rat cardiac membranes were investigated. In vitro, HI-42 displaced 3H-DHA from specific binding sites on the membranes in a non-competitive, reversible manner, yielding Ki-values of 43 and 1626 nmol/l for beta 1- and beta 2-receptors, respectively. After pretreatment in vivo with a single dose of 40 mg/kg HI-42 i.p., the apparent number of beta-adrenoceptors (Bmax of specific 3H-DHA binding) was significantly reduced for up to 4 days, whereas the affinity of the 3H-DHA binding sites (KD) remained unaffected. Similarly as in the in-vitro experiments, the beta-adrenoceptor blocking compound could be removed also after in-vivo pretreatment by extensive washing of the membranes. It is proposed that the long duration of action of HI-42 in vivo is due to the formation of a tight complex with beta 1-adrenoceptors; the bulky lipophilic part of the HI-42 molecule may be responsible for its slow dissociation from the receptor.

Adrenergic beta-Antagonists↗
PubMed1985

Formation and functions of prostaglandins in the central nervous system in rodents.

Electrically- and chemically-induced convulsions, as well as spontaneous convulsions, triggered off a large increase in brain PG synthesis occurring mainly in cerebral cortex and hippocampus. Prevention of PG synthesis by cyclooxygenase inhibitors had no influence on the onset of the first clonic seizure, but markedly reduced the latency time of the final tonic seizure. Accordingly, also the acute toxicity of the convulsant PTZ was enhanced after cyclooxygenase inhibition by various NSAIDs (decrease in LD50). On the other hand, if brain concentrations of prostanoids were increased by a preceding ECS treatment, the onset of PTZ-induced clonic seizures was markedly delayed, and the acute toxicity of the convulsant was reduced. Both effects were abolished after inhibition of PG synthesis. The major cerebral PG formed during convulsions (PGD2) proved to have anticonvulsive properties when injected i.c.v. Also, in convulsion-prone gerbils, anticonvulsive effects of cerebral PGs were observed. These results suggest that endogenously formed brain PGs possess anticonvulsive properties of biological relevance.

Animals↗
PubMed1984

Decreased levels of brain cyclo-oxygenase products as a possible cause of increased seizure susceptibility in convulsion-prone gerbils.

Basal levels of 5 cerebral prostanoids (PGD2, PGF2 alpha, PGE2, 6-keto-PGF1 alpha and thromboxane/TX/B2) were measured radioimmunologically in normal and convulsion-prone gerbils. Significantly less PGD2,PGE2 and 6-keto-PGF1 alpha was found in the brain of seizure-sensitive animals. After treatment with indomethacin, which reduced the amount of brain cyclo-oxygenase products, also normal gerbils exhibited convulsions following environmental stress. The results are in accordance with the hypothesis that endogenous prostanoids play a role in the regulation of seizure susceptibility.

Alprostadil↗
PubMed1984

Endogenous adenosine as a modulator of hippocampal acetylcholine release.

Modulation of acetylcholine release via adenosine receptors was studied in rabbit hippocampal slices, which were preincubated with 3H-choline and then continuously superfused. Electrical field stimulation of the slices elicited a release of acetylcholine, which was inhibited in a concentration-dependent manner by various adenosine receptor agonists. The effects of the agonists were antagonized by the methylxanthines. From the order of potency: cyclohexyladenosine greater than (-)phenylisopropyladenosine [-)PIA) greater than 5'-N-ethylcarboxamideadenosine (NECA) greater than 2-chloradenosine greater than (+)phenylisopropyladenosine greater than adenosine, the inhibitory adenosine receptor may be classified as A1-(R1-)receptor. In experiments on rabbit caudate nucleus slices, adenosine receptor agonists only slightly decreased the evoked acetylcholine release. The presence of an inhibitory tone of endogenous adenosine on hippocampal acetylcholine release is supported by the following findings: 1) the methylxanthines theophylline, 8-phenyltheophylline and 3-isobutylmethylxanthine (IBMX) increased the evoked acetylcholine release in concentrations below those required for phosphodiesterase inhibition. 2) Adenosine uptake inhibitors, in contrast, decreased the evoked transmitter release. 3) Deamination of endogenous adenosine by addition of adenosine deaminase to the medium enhanced the acetylcholine release. In conclusion, acetylcholine release in the hippocampus is depressed at the level of the cholinergic nerve terminals by endogenous adenosine via A1-(R1-)receptors.

1-Methyl-3-isobutylxanthine↗