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K Starke

Publications and source records attributed to K Starke.

At least 217 records · Page 12Linked to original sources
PubMed1982

Non-competitive interaction between normorphine and calcium on the release of noradrenaline.

The interaction between calcium and magnesium or normorphine was studied on the electrically evoked outflow of previously incorporated [3H]noradrenaline in the isolated mouse vas deferens. The stimulation-evoked outflow of [3H]noradrenaline increased with increasing concentrations of Ca2+ ions in the medium. Mg2+ counteracted the effect of Ca2+ in a manner compatible with competitive antagonism. In contrast, normorphine interfered with the effect of Ca2+ non-competitively, thus suggesting that its mode of action differed from that of Mg2+.

Animals↗
PubMed1982

Fate of [3H]amezinium in sympathetically innervated rabbit tissues.

Perfused rabbit hearts accumulated intra-aortically infused [3H]amezinium. At concentrations of 1 or 10 nM, the accumulation proceeded at a constant rate for at least 60 min. After 60 min, tissue medium ratios were between 6 (1 microM) and approx. 100 (1 or 10 nM [3H]amezinium). Cocaine or pretreatment with 6-hydroxydopamine abolished, and pretreatment with reserpine reduced the accumulation of [3H]amezinium (1 nM). Kinetic analysis yielded a Km value of 0.9 microM and a Vmax of 1.2 nmole g-1 min-1. When hearts had been labelled with 1 or 10 nM [3H]amezinium, the fractional rate of the subsequent efflux was very low (0.001 min-1). It was greatly increased when the animals had been pretreated with reserpine. Electrical stimulation of the sympathetic nerves released [3H]amezinium from pre-labelled rabbit pulmonary artery strips. The electrically evoked overflow was abolished by tetrodotoxin or omission of Ca2+; it was enhanced by cocaine, desipramine and yohimbine and decreased by clonidine. The results show that amezinium, at least at low concentrations, is selectively taken up released by action potentials. Amezinium is a structurally novel substrate of both the noradrenaline transport mechanism of the axolemma and the transport mechanism of the noradrenaline-storing synaptic vesicles.

Animals↗
PubMed1982

alpha-Adrenoceptor-mediated inhibition of noradrenaline release in rabbit brain cortex slices. Receptor properties and role of the biophase concentration of noradrenaline.

Brain cortex slices from rabbits were preincubated with [3H]noradrenaline and then superfused and stimulated electrically at 3Hz. In the presence of cocaine 30 microM, unlabelled noradrenaline, alpha-methylnoradrenaline, clonidine, oxymetazoline, xylazine and guanabenz decreased, whereas yohimbine, corynanthine, phentolamine, tolazoline and azapetine increased the stimulation-evoked overflow of tritium. Phenylephrine and prazosin had no effect on the evoked overflow except at concentrations that greatly accelerated the basal outflow of tritium. The results indicate that the noradrenergic axons of rabbit brain cortex are endowed with presynaptic alpha-adrenoceptors which are exclusively of the alpha 2-type. Addition of various concentrations of cocaine, addition of pargyline, or stimulation at different current strengths was used to obtain either a high or low stimulation-evoked overflow of tritium. Independently of the method used, a low evoked overflow coincided with a large percentage inhibition produced by 0.1 micro M clonidine, whereas a high evoked overflow coincided with a smaller percentage inhibition produced by clonidine. The results indicate that drugs which block the re-uptake of noradrenaline diminish the presynaptic inhibitory effect of alpha-adrenergic agonists by increasing the biophase concentration of released noradrenaline.

Adrenergic alpha-Agonists↗
PubMed1982

Metabolism of endogenous and exogenous noradrenaline in the rabbit perfused heart.

The outflow of noradrenaline, 3,4-dihydroxyphenylglycol (DOPEG) and 3,4-dihydroxymandelic acid (DOMA) from rabbit perfused hearts was studied by chromatography on alumina followed by high pressure liquid chromatography with electrochemical detection. In the absence of drugs and without nerve stimulation, the outflow of endogenous noradrenaline over a period of 108 min averaged 0.17 pmol X g-1 X min-1 and the outflow of DOPEG 2.1 pmol X g-1 X min-1. The outflow of DOMA was below the detection limit (less than 0.13 pmol X g-1 X min-1). The effect of perfusion with (-)-noradrenaline 0.1, or 10 mumol/l for 18 min was then investigated. As the concentration of nor-adrenaline increased so did the outflow of DOPEG. Moreover, DOMA was found in the venous effluent during and after perfusion with noradrenaline 1 or 10 mumol/l. The increase in the outflow of DOPEG and DOMA was almost abolished when cocaine 10 mumol/l was present during the perfusion with noradrenaline 1 mumol/l. The release of endogenous noradrenaline by sympathetic nerve stimulation or tyramine 10 mumol/l, but not the release evoked by nicotine 30 mumol/l, was accompanied by an increase in the outflow of DOPEG; an outflow of DOMA was not observed. It is concluded that, in the rabbit perfused heart, DOPEG is an important metabolite of endogenous noradrenaline. DOMA is at best a minor product, either when the neurones are at rest or when noradrenaline is released by sympathetic nerve stimulation, nicotine or tyramine. DOMA is formed in detectable amounts when the tissue is exposed to a high concentration of exogenous noradrenaline. Like DOPEG, it is formed intraneuronally. The results confirm and extend those obtained previously on guinea-pig incubated atria. They make it unlikely that, in these tissues at least, DOMA formation is one of the physiological pathways of noradrenaline catabolism.

Animals↗
PubMed1982

The noradrenaline rate in the anaesthetized rabbit: facilitation by adrenaline.

1. 3H-Noradrenaline was infused intravenously into pentobarbitone anaesthetized rabbits to reach a steady-state plasma 3H-noradrenaline level, from which the noradrenaline plasma clearance was calculated. The plasma level of endogenous noradrenaline was determined simultaneously and the rate of noradrenaline release was then derived. 2. Pargyline, amezinium, desipramine and guanethidine all reduced the noradrenaline plasma clearance. The noradrenaline release rate was decreased by desipramine, guanethidine and clonidine. 3. Adrenaline (6 nmol/kg i.v. twice) enhanced the noradrenaline release rate by 53%. This effect was apparent after the plasma adrenaline has returned to basal levels. The adrenaline levels in sympathetically innervated tissues were elevated at this time. 4. When the rabbits were pretreated with either propranolol HCl (1 mg/kg i.p.) to block beta-adrenoceptors, or desipramine HCl (1 mg/kg i.v.) to block neuronal uptake, the facilitatory effect of adrenaline was abolished. Noradrenaline (6 nmol/kg i.v. twice) had no effect on the noradrenaline release rate. 5. These findings suggest that if the sympathetic transmitter stores contain sufficient adrenaline neuronally released adrenaline may modulate noradrenaline release in vivo by activating facilitatory presynaptic beta-adrenoceptors.

Anesthesia↗
PubMed1982

Are presynaptic dopamine autoreceptors and postsynaptic dopamine receptors in the rabbit caudate nucleus pharmacologically different?

Slices of the rabbit caudate nucleus were preincubated with [3H]dopamine or [3H]choline and then superfused and stimulated electrically. Apomorphine reduced the stimulation-evoked overflow of tritium over the same concentration range, independently of whether slices had been pre-incubated with [3H]dopamine or with [3H]choline. Each of three antagonists--molindone, sulpiride and metoclopramide--increased the evoked overflow of tritium over the same concentration range in experiments with [3H]dopamine and those with [3H]choline. For each antagonist, the pA2 values against apomorphine obtained in [3H]dopamine experiments and in [3H]choline experiments were very similar. This study is a functional in vitro approach to receptor characterization, as opposed to radioligand binding studies or in vivo investigations. The results show that the dopamine receptor agonist apomorphine and three antagonists are unable to distinguish between the presynaptic, release-inhibiting dopamine autoreceptors and those postsynaptic dopamine receptors which, when activated, depress the release of acetylcholine. Although there are certainly more dopamine receptors in the caudate nucleus, these two physiologically important groups seem to be closely related.

Acetylcholine↗
PubMed1982

Types and functions of peripheral alpha-adrenoceptors.

Both in the periphery and in the central nervous system, alpha-adrenoceptors can be subdivided into alpha 1-types. alpha 1-Receptors are sensitive to low concentrations of the agonists phenylephrine and methoxamine, and of the antagonists corynanthine and prazosin. alpha 1-Receptors are sensitive to low concentrations of the agonists clonidine and tramazoline, and of the antagonists yohimbine and rauwolscine. Although it has been shown recently that some smooth muscle tissues contain postsynaptic, contraction-mediating alpha 2-adrenoceptors, the smooth muscle of rabbit aorta and pulmonary artery possesses only alpha 1-receptors. In rabbit portal vein, practically all of the effect of exogenous agonists is mediated by alpha 1-receptors. On the other hand, prazosin resistance and rauwolscine sensitivity of the contractile response to transmural sympathetic nerve stimulation indicates that released noradrenaline may act on a small population of postsynaptic alpha 2-receptors as well.

Animals↗
PubMed1982

Gamma-aminobutyric acid can both inhibit and facilitate dopamine release in the caudate nucleus of the rabbit.

Slices from rabbit caudate nucleus were preincubated with [3H]dopamine and then superfused and stimulated electrically. gamma-Aminobutyric acid (10-4) and 10(-3) mol/L increased both the basal and the stimulation-evoked overflow of tritium. The effects were not changed by picrotoxin and were only slightly reduced by bicuculline. In the presence of nipecotate 10(-3) mol/L, gamma-aminobutyric acid decreased rather than enhanced the basal and the evoked overflow. The inhibition persisted in the presence of bicuculline. Muscimol did not affect, whereas baclofen decreased, the evoked overflow of tritium. Similar results obtained with synaptosomes that were stimulated by 30 mmol/L K+. The results indicate that gamma-aminobutyric acid can both facilitate and depress the release of dopamine. Facilitation occurs after entry of gamma-aminobutyric acid into the dopaminergic terminal axons, whereas inhibition if probably mediated by a receptor site located in the membrane of these terminals.

Animals↗
PubMed1982

An examination of the pre- and postsynaptic alpha-adrenoceptors involved in neuroeffector transmission in rabbit aorta and portal vein.

1 The alpha-adrenoceptor agonists, clonidine and xylazine, reduced and the alpha-antagonists, yohimbine an rauwolscine, increased the stimulation-evoked tritium overflow from rabbit aorta and portal vein pre-incubated with [3H]-noradrenaline. 2 Based on an order of agonist potency of clonidine greater than xylazine greater than phenylephrine and antagonist potency of rauwolscine = yohimbine greater than prazosin, the presynaptic receptor mediating these effects is of the alpha 2 type. 3 In the aorta, stimulation-evoked contractions were abolished by prazosin (0.1 micrometers) and potentiated by rauwolscine and yohimbine in concentrations that increased the stimulation-evoked overflow tritium. 4 In the portal vein, prazosin was less potent in reducing, and rauwolscine and yohimbine failed to potentiate, the stimulation-evoked contraction. 5 In experiments in which tissues were pre-exposed to phenoxybenzamine (30 nM) to block some of the postsynaptic alpha-receptors, rauwolscine in concentrations that increased stimulation-evoked tritium overflow, reduced the evoked contraction in the portal vein but not in the aorta. 6 It is concluded that presynaptic alpha 2-autoreceptors are present in both tissues and that the postsynaptic alpha-receptors which mediate nerve stimulation-evoked contractions are alpha 1 in the aorta but a mixture of alpha 1 and alpha 2 in the portal vein.

Animals↗
PubMed1982

Effects of 4-chloro-2-(2-imidazolin-2-ylamino)-isoindoline Hydrochloride (BE 6143) at pre- and postsynaptic alpha-adrenoceptors in rabbit aorta and pulmonary artery.

Strips of rabbit aorta and pulmonary artery were used to study the effects of 4-chloro-2-(2-imidazolin-2-ylamino)-isoindoline hydrochloride (BE 6143 or BDF 6143) on pre- and postsynaptic alpha-adrenoceptors. BE 6143 caused contraction of both preparations with a potency slightly higher than and an intrinsic activity 0.7-0.8 that of phenylephrine. The effect was competitively antagonized by prazosin and rauwolscine. Conversely, BE 6143 antagonized contractile responses to phenylephrine, alpha-methylnoradrenaline and noradrenaline (norepinephrine) with pA2 values of 7.1-7.4. In strips preincubated with 3H-noradrenaline and then superfused, BE 6143 increased the electrically evoked overflow of tritium. Increases by 30% were produced by concentrations of about 1.5 nmol/l; high concentrations failed to change or even reduced the evoked overflow. BE 614 0.01 mumol/l also increased electrically evoked contractions whereas high concentrations were inhibitory. The drug shifted the log concentration-response curve of clonidine for inhibition of evoked tritium overflow to the right in parallel manner; from the shift, a pA2 value of 8.3 was calculated. When presynaptic alpha-adrenoceptors had been blocked by yohimbine or rauwolscine, BE 6143 0.01-10 mumol/l caused a decrease in evoked tritium overflow which was more pronounced, the higher the concentration of yohimbine or rauwolscine. It is concluded that BE 6143 acts as a partial agonist at the postsynaptic alpha 1-adrenoceptors and as an antagonist at the presynaptic alpha 2-receptors of rabbit aorta and pulmonary artery. It has higher affinity pre- than postsynaptically, and its affinity for the presynaptic receptors exceeds that of yohimbine and rauwolscine. In addition, however, BE 6143 inhibits the release of noradrenaline by a non-alpha-adrenergic mechanism.

Animals↗
PubMed1981

Functional characterization of central alpha-adrenoceptors by yohimbine diastereomers.

Rat occipital cortex slices were preincubated with [3H]noradrenaline and then superfused with medium containing 30 micrometer cocaine. They were stimulated electrically at 3 Hz. Unlabelled noradrenaline (0.1 micrometer), alpha-methyl-noradrenaline (0.01-0.1 micrometer), xylazine (0.1-10 micrometer) and guanabenz (0.01 micrometer) decreased, whereas yohimbine (0.01-1 micrometer), rauwolscine (0.01-1 micrometer), corynanthine (10 micrometers), tolazoline (0.1-10 micrometers) and azapetine (0.1-1 micrometer) increased the stimulation-evoked overflow of tritium without a change in basal outflow. Pseudoyohimbine and prazosin at up to 0.1 micrometer did not change the evoked overflow, and a higher concentrations enhanced the basal outflow of tritium. In vivo, yohimbine 10 mg/kg and rauwolscine 10 mg/kg markedly, and corynanthine 10 mg/kg slightly accelerated the alpha-methyltyrosine-induced disappearance of noradrenaline from rat whole brain. Yohimbine and rauwolscine but not corynanthine also accelerated the alpha-methyltyrosine-induced depletion of dopamine. The results add four compounds to the list of drugs with alpha-adrenoceptor affinity which inhibit (agonists) or facilitate (antagonists) action-potential-evoked release of noradrenaline in rat brain cortex. The presynaptic receptors are of the alpha 2-type. The receptors which control the activity of noradrenaline and dopamine neurons in vivo also appear to be alpha 2.

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

[Roentgen diagnosis of the large intestine with special reference to the double-contrast method and its significance in tumor diagnosis].

In the X-ray examination of the large intestine by means of the retrograde contrast medium enema on extreme filling radiographs as well as on radiographs of the mucous membrane small tumours can be overseen. The same applies to the peroral demonstration of the large intestine. Better results are yielded by the double contrast method. Therefore it has been exclusively used in our clinic since 1961. The following prerequisites must be fulfilled for an evident examination: - optimum cleaning of the bowel, - steady and thin contrast medium covering of the intestinal wall and demonstration of all sections of the intestine on 2-3 pictures in different position of the radiograph in every case. Under these conditions polyps of a diameter of 5-6 mm can be demonstrated. With the help of results of the examinations of 1,390 patients it is referred to the importance of the demonstration also of small lesions of the colon. The rate of carcinomas amounted to 14,5%; that of polyps was 6,2%. For 1/5 of the polyps a malignancy was determined histologically.

Adult↗
PubMed1981

Metabolism of endogenous and exogenous noradrenaline in guinea-pig atria.

The outflow of noradrenaline, 3, 4-dihydroxy-phenylglycol (DOPEG) and 3, 4-dihydroxymandelic acid (DOMA) from guinea-pig isolated atria was studied by chromatography on alumina followed by high pressure liquid chromatography with electrochemical detection. In the absence of drugs, the outflow of endogenous noradrenaline over a period of 3 h averaged 1.6 pmol x g-1 x min-1 and the outflow of DOPEG 17 pmol x g-1 x min-1. The outflow of DOMA was below the detection limit (less than 0.31 pmol x g-1 x min-1). Tyramine greatly increased the outflow of noradrenaline and DOPEG, and the reserpine-like compound Ro4-1284 selectively increased the outflow of DOPEG; DOMA remained below the detection limit. When atria were exposed to (-) noradrenaline 1.7 or 17 microM, the subsequent outflow of noradrenaline and DOPEG was enhanced. Moreover, substantial amounts of DOMA were now found. This outflow of DOMA was prevented when atria were exposed to (-) noradrenaline in the presence of cocaine or after an initial incubation with amezinium. Exposure to (-)-noradrenaline 1.7 microM mainly enhanced the formation of DOPEG, while exposure to (+)-noradrenaline 1.7 microM mainly enhanced the formation of DOMA. Our experiments confirm some and qualify other conclusions drawn from studies in which exogenous 3H-noradrenaline had been used to examine the metabolism of noradrenaline in guinea-pig atria. In agreement with the isotope studies, DOPEG is a major metabolite of endogenous noradrenaline. In contrast to what the isotope studies had suggested, however, endogenous DOMA is a very minor product, at least as long as the neurones are at rest. DOMA is only formed when the tissue is exposed to high concentrations of exogenous noradrenaline. In further contrast to previous conclusions, DOMA is then formed intra- and not extraneuronally.

Animals↗
PubMed1981

Pathways of dopamine metabolism in the rabbit caudate nucleus in vitro.

Slices of rabbit caudate nucleus were preincubated with 3H-dopamine and then superfused. 3H-dopamine and its metabolites were separated by column chromatography. The basal outflow of tritium consisted of 68% DOPAC, 21% OMDA metabolites (most of which was HVA), 6% dopamine and 5% MTA. Except for an increase in 3H-dopamine, the basal outflow was little changed by nomifensine or cocaine. Amezinium reduced the outflow of 3H-DOPAC and 3H-OMDA metabolites and increased that of 3H-dopamine and 3H-MTA; its effect was antagonized by nomifensine. Haloperidol 10(-7) M selectively enhanced the outflow of 3H-DOPAC and 3H-OMDA metabolites. At haloperidol 10(-5) M, a large increase in these two fractions was accompanied by a small increase in 3H-dopamine and 3H-MTA. Nomifensine diminished only slightly the outflow of 3H-DOPAC caused by haloperidol. The overflow of tritium elicited by electrical stimulation at 3 Hz consisted of 74% DOPAC, 15% OMDA metabolites, 10% dopamine and 0.4% MTA. Lowering the frequency reduced the overflow of total tritium and caused a decrease in the percentage of 3H-DOPAC and an increase in the percentage of 3H-dopamine. Nomifensine or cocaine greatly diminished the evoked overflow of 3H-DOPAC and 3H-OMDA compounds and increased the evoked overflow of 3H-dopamine and 3H-MTA. The effects of apomorphine and bromocriptine were similar to those caused by decreasing the stimulation frequency. The major pathways of the metabolism of previously taken up dopamine, under the conditions of our experiments, are as follows. When the neurones are at rest, dopamine metabolism is initiated by leakage of the amine into the axoplasm, where it is degraded through the aldehyde to DOPAC. Part of the DOPAC is methylated extraneuronally to HVA. Traces of MTA are formed by extraneuronal methylation of dopamine. When action potentials arrive, dopamine metabolism is initiated by exocytosis. The bulk of the extracellular dopamine is taken up back into the neurones. When the stimulation frequency is 3 Hz, most of the axoplasmic dopamine is subsequently transformed to DOPAC; little seems to be re-stored. HVA and MTA are generated essentially as during neuronal rest. When dopamine release is low (stimulation at low frequency; addition of apomorphine or bromocriptine), a larger portion seems to be re-stored, thus leading to a decrease in the percentage of DOPAC. Haloperidol, apart from its receptor blocking properties, acts on dopaminergic axons in a manner akin to the effect of reserpine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Smooth muscle of rabbit aorta contains alpha 1-but not alpha 2-adrenoceptors.

We have investigated the residual contractile response to noradrenaline remaining after phenoxybenzamine (3 x 10(-7) mol/l) in rabbit aorta, since it has been reported that phenoxybenzamine at low doses completely and irreversibly blocks alpha 1-but not alpha 2-adrenoceptors. The contraction elicited by noradrenaline slowly recovered with time after it had been almost abolished by phenoxybenzamine. This residual response was blocked by the alpha 1-selective antagonist prazosin (3 x 10(-8) mol/l) but not by the alpha 2-selective antagonist rauwolscine (3 x 10(-7) mol/l). The results confirm that the smooth muscle of rabbit aorta contains alpha 2-but not alpha 2-adrenoceptors.

Animals↗