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Biomedical subjects

T Ott

Publications and source records attributed to T Ott.

At least 55 records · Page 3Linked to original sources
PubMed1992

Studies with new ergoline derivatives on the effects of central and peripheral 5-hydroxytryptamine receptors.

The antiserotonin properties of a series of new ergoline derivatives were investigated in several pharmacological test systems which have been proposed for the characterization of putative antagonists at central and peripheral 5-HT2 receptors. In radioligand binding studies with [3H]ketanserin among the new ergolines only 1-methyl-2-brom-9,10-dihydrolysergic acid-bis(beta-acetoxyethyl)-amide (AWD 52-336) showed high affinity at cortical 5-HT2 receptors (Ki-5.4 nmol/l). In 5-HT-amplified ADP-induced aggregation of human platelets 6-nor-6-propyl-9,10-dihydro ergometrine (AWD 52-227) and 9,10-dihydrolysergic acid-di-ethanol-amide (AWD 52-302) were potent inhibitors of 5-HT response. Comparison of this two in vitro tests demonstrated a significant correlation (r = 0.636; p < 0.05) between the ability of the ergolines to block the 5-HT aggregation mediated by platelet 5-HT2 receptors and their affinity to [3H]ketanserin-labelled binding sites in rat cortical membranes. In the used in vivo tests (tryptamine tremor, 5-HTP-induced head twitches) 1-methyl-9,10-dihydrolysergic acid-bis(beta-acetoxyethyl)-amide (AWD 52-83) and AWD 52-336 were found to antagonize the behavioural responses with comparatively moderate potency. The results suggest, therefore, that AWD 52-83 and AWD 52-336 may be both central and peripheral acting 5-HT2 antagonists, whereas AWD 52-227 and AWD 52-302 seem to be potent blockers at peripheral 5-HT2 receptors. Furthermore, the obtained results allow to reveal structure-activity relationships of ergolines. Substitution in position 1 in the tetracyclic ergoline ring system may be important with respect to the efficacy at central 5-HT2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Hydroxytryptophan↗
PubMed1991

CCK-8-related C-terminal tetrapeptides: affinities for central CCKB and peripheral CCKA receptors.

We investigated the binding affinity of new tetrapeptides derived from the C-terminal sequence of CCK8 to central CCKB and peripheral CCKA receptors. Compound 1 (Boc-Trp-Met-Asp-Phe-NH2) showed high affinity for central CCKB receptors (Ki 4.2 x 10(-8) M, pancreas/cortex ratio = 283). Compounds 2 (Suc-Trp-Met-Asp-Phe-NH2) and 3 (Suc-Trp-Leu-Asp-Phe-NH2) also exhibited high affinity (Ki 2.7 x 10(-8) M and 5.6 x 10(-8) M, respectively) but their CCKB selectivity was nearly 50 times higher (Ki ratio greater than 14,000). Replacement of Met or Leu by other amino acids resulted in less effective tetrapeptides.

Amino Acid Sequence↗
PubMed1991

Diminished synaptosomal dopamine (DA) release and DA autoreceptor supersensitivity in schizophrenia.

Post-mortem brain regions of schizophrenics were investigated in comparison to matched controls regarding synaptosomal K(+)-stimulated [3H]DA release and its modulation by DA autoreceptors. Brain specimens were cryopreserved in liquid nitrogen until release experiments; synaptosomes from brain pieces preincubated with dimethylsulfoxide have unchanged ability for [3H]DA release and its autoreceptor-mediated inhibition after cryo-preservation. Release data were individually corrected for post-mortem delay back to the zero-time state based on [3H]DA release alterations after in situ preservation of rat heads. In schizophrenia, the K(+)-stimulated [3H]DA release from superfused synaptosomes of the nucleus (n.) accumbens and n. caudatus was diminished significantly. Furthermore, functional supersensitivity of the modulatory DA autoreceptors could be demonstrated in these regions. The alterations demonstrated seem not to be due primarily to medication since in neuroleptic-free patients similar changes were shown.

Amygdala↗
PubMed1991

2-Bromolisuride, an ergot derivative, with dopamine antagonistic and serotonin agonistic properties.

The open-field test was used to study the involvement of dopaminergic and serotonergic mechanisms in the effects of 2-bromolisuride on locomotor activity in the rat. 2-Bromolisuride produced a dose-dependent inhibition of spontaneous locomotor activity. This is most likely due to an antagonistic action at postsynaptic dopamine receptors. Low doses of 2-bromolisuride potentiated apomorphine-induced hypermotility. This potentiating effect was not mediated by a blockade of presynaptic dopamine receptors, because it was not prevented by 6-OHDA lesion of the nucleus accumbens. The potentiating effect of 2-bromolisuride was completely blocked by the serotonin antagonists cyproheptadine and ritanserin. It is suggested that 2-bromolisuride possesses dopamine antagonistic and serotonin agonistic properties.

Animals↗
PubMed1991

CCK-8 modulates D2 receptor agonist-induced hypermotility in the nucleus accumbens.

The influence of CCK-8 on locomotor effects associated with independent D2 receptor stimulation was studied. To selectively stimulate mesolimbic D2 receptors LY 171555 was injected into the nucleus accumbens of awake rats. Locomotor activity was measured in the open-field test. LY 171555 induced a biphasic effect: low doses stimulated, whereas higher doses inhibited locomotor activity. CCK-8 injected into the posteromedial part of the nucleus accumbens suppressed hyperlocomotion induced by LY 171555. The CCK-8 effect was prevented by the CCK-antagonist L 364,718. Our results indicate that CCK-8 modulates D2 receptor-mediated effects in the mesolimbic system.

Animals↗
PubMed1991

Comparison of two syphilis antibody assays based on cardiolipin antigen.

Two different antisyphilis screening tests based on cardiolipin antigen, the VDRL test and an RPR test (Sysmic, Diagast), were compared. A total of 2155 sera were examined by both tests. Positive results were confirmed with TPHA and TPI tests. RPR Sysmic test was as sensitive and specific as the VDRL. However, the RPR Sysmic test was easier and quicker, especially when the number of sera tested was high.

Antibodies, Bacterial↗
PubMed1990

The influence of tifluadom on cholecystokinin-induced antinociception.

The effects of tifluadom, a benzodiazepine-kappa-opioid-receptor agonist, on cholecystokinin-octapeptide (CCK-8)-induced antinociception were investigated in the mouse writhing test. When given alone, tifluadom produced pronounced, dose-dependent analgesia. The antinociceptive effect of intracerebroventricularly injected CCK-8 was potentiated by high doses of tifluadom. In contrast, when tifluadom was applied at low doses which did not induce antinociception, the antinociceptive effect of CCK-8 was completely antagonized. It is concluded that tifluadom acts both as kappa-opioid receptor agonist and as an antagonist at CCK receptors mediating CCK-induced antinociception.

Analgesics↗
PubMed1990

Atypical neuroleptics suppress dopaminergic behavioral supersensitivity.

Seven days after bilateral 6-OHDA denervation of the nucleus accumbens locomotor activity was recorded in rats. 6-OHDA lesion strongly enhanced hypermotility induced by apomorphine (1.0 mg/kg IP) as a sign of behavioral dopaminergic supersensitivity. The potency of the classical neuroleptic haloperidol (0.03-0.25 mg/kg IP) to antagonize apomorphine-induced hypermotility was reduced in 6-OHDA-pretreated rats. The atypical neuroleptics sulpiride (5.0-20.0 mg/kg IP), thioridazine (1.0-5.25 mg/kg IP) and clozapine (0.5-2.0 mg/kg IP) and the 5-HT antagonists cyproheptadine (0.2 mg/kg IP) and ritanserin (0.01 mg/kg IP) suppressed the augmented apomorphine response in 6-OHDA-lesioned animals to the level of the apomorphine effect in controls. It is concluded that the model of denervation supersensitivity is capable of differentiating typical and atypical neuroleptics. The abolition of the 6-OHDA-induced increase of the apomorphine hypermotility by the atypical neuroleptics cannot be explained solely by postsynaptic dopamine receptor antagonism. Serotonergic mechanism may be involved in this action.

Animals↗
PubMed1989

Sexually dimorphic level of CCK-8-like immunoreactive neuronal somata within several basal forebrain nuclei of the rat.

Using indirect immunocytochemical technique CCK-8-like immunoreactive somata could be demonstrated in different basal forebrain nuclei of adult rat (olfactory tubercle, nucleus accumbens septi, nucleus tractus diagonalis BROCA, nucleus septi medialis et lateralis, caudate-putamen-complex). The comparison of these findings with those of rapid Golgi technique and AChE histochemistry suggested that all CCK-8 immunostaining nerve cells should be aspiny neurons and, partly at least, a coexistence of CCK-8 and acetylcholine is assumed. In the number of neuronal somata with CCK-8-like immunoreactivity in all nuclei, especially in the caudate-putamen-complex, a distinct difference between male and female rats exist.

Animals↗
PubMed1989

[Cholecystokinin-8-like immunoreactive structures in the olfactory bulb of the rat].

Using indirect immunocytochemical technique CCK-8-like immunoreactive neuronal somata and nerve fibers could be demonstrated in the olfactory tubercle of the rat. Cells found by immunostaining were compared with neuron types visible in Golgi-rapid-preparations. The existence of a CCK-containing efferent neuron type in the olfactory tubercle of the rat is suggested.

Animals↗
PubMed1987

[Cholecystokinin-peptides--new knowledge and possibilities for clinical use].

This issue comprises selected topics of CCK peptides. CCK peptides are linear peptides and were found within and outside the CNS. There is growing evidence that CCK peptides play a physiological role in food intake, contraction of gallbladder and regulation of motility of the gastrointestinal system. New aspects of the CCK research are concentrated on interaction with other transmitter systems especially with the dopamine and opioid system. The therapeutic action to improve clinical symptoms in human is unclear up to new. World-wide, the interest is focused to determine the potential of CCK peptides as an antipsychotic agent by controlled clinical studies.

Animals↗
PubMed1987

Cerebroventricular infusion of cholecystokinin (CCK-8) restores REM sleep in parachlorophenylalanine (PCPA)-pretreated cats.

Recently, some studies have shown that cholecystokinin (CCK-8) administered either intraventricularly or intraperitoneally has no effect on sleep. However, since in such studies CCK-8 was given at times when sleep predominates, in this study the effects of CCK-8 on sleep were determined in parachlorophenylalanine (PCPA) (400 mg/kg)-pretreated insomniac cats. Twenty-four hours after the second injection of PCPA one group of cats received 100 ng/100 microliter of CCK-8 and another group only 100 microliter of saline. A third group was studied only under the effects of PCPA. The results showed that CCK-8 was capable of restoring sleep in the otherwise insomniac cats and that this effect was restricted to REM sleep only. The observed REM sleep-promoting action of CCK-8 supports the notion that this polypeptide may be involved in REM sleep regulation.

Animals↗
PubMed1986

Low frequency perforant path stimulation as a conditioned stimulus demonstrates correlations between long-term synaptic potentiation and learning.

Stimulation of the perforant path with impulse trains of 15 cps and 670 msec duration was used as a conditioned stimulus in a two-way shuttle box avoidance on rats. Field potentials in the dentate area evoked by test stimuli were measured after the training sessions until the 7th day. Foot-shock and unconditioned escape elicited only a transient slight depression of the population spike amplitude (P) and increased also slightly the slope function (SF) of the population EPSP of the evoked test potentials. The control stimulation of the perforant path without pairing with foot-shock as in conditioning did only slightly increase SF of test potentials, but produced a strong transient inhibition followed by a long lasting moderate depression of P. After conditioning, all animals exhibited the same initial inhibition of P as shown in control stimulation of the perforant path. However during the following 4 hours, good learners with a relearning index greater than 30% developed a significant potentiation of P lasting until the second training session 24 hours later, which resulted in a further enhancement. SF of the evoked test potentials increased in good learners with a similar time course after conditioning but without initial depression. After 7 days P showed still enhanced but non-significant values. Poor learners with a relearning index less than 10% did not develop a potentiation of P after conditioning and initial inhibition, but a long-term depression. Also SF of test potentials decreased in poor learners during 4 hours after conditioning and returned almost to baseline until the following day. After 7 days, P and SF did not differ from baseline. The analysis of the observed synaptic changes by E-S curves demonstrated the post-tetanic LTP seems to differ in some ways from post-conditioning LTP in good learners. The latter exhibits a clear tendency of a right shift contrary to the left shift commonly occurring after tetanization. Furthermore poor learners do not only fail to produce long-term potentiation, but fail to show a change in the opposite direction with a left shift of the E-S curves. The observed correlation of LTP in the conditioning pathway with the learning ability suggests an involvement of LTP at least in the acquisition and early retention of this learned behavior. The results do however not finally clarify the role of LTP in long-term retention.

Animals↗
PubMed1986

Opioid-receptor blockade reduces nose-poke self-stimulation derived from medial entorhinal cortex.

Rats were trained to nose-poke for intracranial self-stimulation (SS) with electrodes unilaterally implanted in the medial entorhinal cortex. The acute effects of naloxone (NX; 0.1-10 mg/kg, IP) on a continuous reinforcement schedule were determined. Reductions in the self-stimulation rates occurred only at moderate doses (median of individual changes = -36% at 1 and 5 mg/kg), whereas the high dose (10 mg/kg) was ineffective. None of the doses influenced operant behavior. These results are consistent with the hypothesis that endogenous opioid-opiate receptor mechanisms play a modulatory role in SS reward. Considering that NX was administered systemically the action of the drug on reinforcement levels may be mediated by a site distinct from the locus of stimulation.

Animals↗