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Biomedical subjects

K Starke

Publications and source records attributed to K Starke.

At least 91 records · Page 5Linked to original sources
PubMed1995

Involvement of monoamine uptake inhibition and local anesthesia in the cardiovascular response to cocaine in conscious rabbits.

The cardiovascular effect of cocaine in rabbits was examined for peripheral and central components and for the contribution of the primary actions of cocaine, i.e., inhibition of the high affinity uptake mechanisms for monoamines and local anesthesia. In pithed rabbits with electrically stimulated sympathetic outflow (2 Hz), cocaine (0.2-5 mg kg-1) lowered the clearance of [3H]norepinephrine from plasma and increased the plasma norepinephrine concentration. Cocaine (0.2 and 1 mg kg-1) increased blood pressure and heart rate, whereas after 5 mg kg-1 heart rate and blood pressure decreased briefly and then recovered. In conscious rabbits, cocaine (0.2 and 1 mg kg-1) reduced renal sympathetic nerve activity and tended to reduce blood pressure and heart rate. Cocaine (5 mg kg-1) increased sympathetic nerve activity, blood pressure and the plasma norepinephrine and epinephrine concentrations. The effects of the lower doses were abolished in animals pretreated with oxaprotiline, but were not changed in animals pretreated with fluvoxamine or SCH 23390 (R-(+)-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol) + sulpiride. The effects of cocaine (5 mg kg-1) were attenuated by SCH 23390 + sulpiride but were not changed after oxaprotiline or fluvoxamine. Procaine (15 mg kg-1) mimicked the effects of cocaine (5 mg kg-1) on blood pressure and renal sympathetic nerve activity. Blood pressure also was increased by lidocaine (6 mg kg-1). It is concluded that cocaine enhances peripheral sympathetic neuro-effector transmission. In conscious rabbits, however, low doses fail to raise blood pressure because they simultaneously depress central sympathetic tone by blockade of the uptake of norepinephrine in the central nervous system. High cocaine doses cause sympathoexcitation in conscious rabbits. The mechanism seems to be dual: blockade of dopamine uptake in the central nervous system and a (peripheral or central) local anesthetic action.

Anesthetics, Local↗
PubMed1994

Modulation of neural noradrenaline and ATP release by angiotensin II and prostaglandin E2 in guinea-pig vas deferens.

Effects of angiotensin II and prostaglandin E2 on contractions, release of noradrenaline and release of ATP elicited by electrical stimulation (210 pulses, 7 Hz) were studied in the isolated vas deferens of the guinea pig. Release of noradrenaline was assessed as overflow of tritium after preincubation with [3H]-noradrenaline. ATP was measured by means of the luciferin-luciferase technique. In some experiments postsynaptic alpha 1-adrenoceptors and P2X-purinoceptors were blocked by prazosin and suramin, respectively, to isolate the neural fraction of the overflow of ATP. Electrical stimulation elicited an overflow of tritium and ATP and, in the absence of prazosin and suramin, contraction. In the absence of prazosin and suramin, angiotensin II (1-100 nM) enhanced contractions as well as the evoked overflow of tritium and ATP. All parameters were increased by about the same percentage for a given concentration of angiotensin II. The effect of prostaglandin E2 (1-100 nM) was complex. Contractions were mainly enhanced, the evoked overflow of tritium was reduced, whereas the evoked overflow of ATP was predominantly increased. No or almost no contraction remained in the presence of prazosin and suramin, and the evoked overflow of ATP was decreased to about 16%. Angiotensin II (1-100 nM) again enhanced the evoked overflow of tritium and ATP. Both were increased by about the same percentage for a given concentration of angiotensin II and also were increased by about the same percentage as obtained in the absence of prazosin and suramin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1994

P2-purinoceptor-mediated autoinhibition of sympathetic transmitter release in mouse and rat vas deferens.

Effects of drugs acting at P2-purinoceptors on the release of newly taken up [3H]-noradrenaline were studied in slices of mouse and rat vas deferens. The slices were superfused and stimulated electrically, in most experiments by trains of 60 pulses/8 Hz. In mouse vas deferens, the P2-purinoceptor antagonists reactive blue 2 (1.8-100 microM) and brilliant blue G (10-300 microM) increased the stimulation-evoked overflow of tritium in a concentration-dependent manner as shown previously for suramin. Reactive blue 2, which preferentially blocks the P2Y-subtype, was the most potent compound and the compound with highest maximal effect, an increase by 104%. Pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), in contrast, caused a small increase only at a single concentration (30 microM). The effects of reactive blue 2, brilliant blue G and suramin were not additive. The P2 agonist adenosine 5'-O-(3-thio)-triphosphate (ATP gamma S) reduced the evoked overflow of tritium. As shown previously for suramin, reactive blue 2 30 microM and brilliant blue G 100 microM antagonized the effect of ATP gamma S. From the shift of the ATP gamma S concentration-response curve to the right, an apparent pKB value of 5.3 was estimated for reactive blue 2 and an apparent pKB of 4.5 for brilliant blue G. In rat vas deferens, reactive blue 2 (3-30 microM), brilliant blue G (10 microM) and suramin (30-300 microM) also increased the evoked overflow of tritium. As in the mouse, reactive blue 2 was the most potent compound and the compound with highest maximal effect, an increase by 90%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Presynaptic alpha 2A-adrenoceptors inhibit the release of endogenous dopamine in rabbit caudate nucleus slices.

alpha 2-Adrenoceptors modulating the release of dopamine were identified and characterized in slices of the head of the rabbit caudate nucleus. Release of endogenous dopamine was measured by fast cyclic voltammetry as the increase in the extracellular concentration of dopamine elicited by electrical stimulation. The electrochemical signal was identified as dopamine by means of the oxidation potential, the voltammogram and the fact that the signal was not changed by desipramine, which inhibits the high affinity uptake of noradrenaline, but was greatly increased by nomifensine, which in addition inhibits the high affinity uptake of dopamine. Stimulation by 6 pulses/100 Hz increased the extracellular concentration of dopamine by about 85 nM. The selective alpha 2-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) reduced this release with an EC50 of 173 nM and by maximally 75%. The alpha 2-adrenoceptor agonists clonidine and oxymetazoline only tended to cause a decrease. Six drugs, including oxymetazoline, were tested as antagonists against UK 14,304. Their order of antagonist potency (pKD values in brackets) was rauwolscine (8.0) > oxymetazoline (7.5) > 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101; 7.3) > phentolamine (7.1) > corynanthine (5.1) approximately prazosin (<6). Given alone, the antagonists did not change the release of dopamine elicited by 6 pulses/100 Hz, and the same was true for the dopamine receptor antagonist sulpiride. When caudate slices were stimulated by 10 pulses/1 Hz, sulpiride increased the release of dopamine. Desipramine and rauwolscine, in contrast, again caused no change. It is concluded that dopaminergic axons in the rabbit caudate nucleus possess release-inhibiting alpha 2-adrenoceptors.2+ off

Adrenergic Agents↗
PubMed1994

The fade of the purinergic neurogenic contraction of the guinea-pig vas deferens: analysis of possible mechanisms.

The purinergic response of the guinea-pig vas deferens to long trains of pulses at high frequency consists of an initial twitch followed by a much lower plateau. Mechanical, neurochemical and electrophysiological techniques were used to examine the reason for the fade. Mechanical measurements. In tissues stimulated by trains of 180 pulses/10 Hz and treated with prazosin to suppress the noradrenergic contraction component, the response to alpha, beta-methylene ATP and to exogenous ATP was as high during the secondary plateau of the purinergic neurogenic contraction as it was outside electrical stimulation periods; the response to 50 pulses/100 Hz was also unchanged during the low plateau. The plateau was not increased by reactive blue 2,8-(p-sulphophenyl)theophylline, propranolol or capsaicin. Neurochemical measurements. In tissues preincubated with [3H]-noradrenaline, electrical stimulation elicited an overflow of tritium and of ATP. In the absence of drugs as well as in the presence of prazosin and suramin to suppress contractions, the overflow of tritium per pulse decreased slightly in the course of trains of 90 pulses/10 Hz; the overflow of ATP per pulse decreased to a greater extent on average, but the decrease was not statistically significant. In the presence of prazosin and nifedipine, also to suppress contractions, the overflow of tritium per pulse again decreased slightly in the course of trains of 105 pulses/10 Hz, but the overflow of ATP per pulse if anything tended to increase. Electrophysiological measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1994

Release of ATP in rat vas deferens: origin and role of calcium.

Release of endogenous ATP elicited by electrical (neural) stimulation and exogenous agonists was studied in the rat isolated vas deferens. The aims were to dissect neural and postjunctional contributions to the nerve activity-evoked overflow of ATP and to clarify the role of transmitter receptors and calcium in postjunctional ATP release. In tissues preincubated with [3H]-noradrenaline, electrical stimulation (100 pulses/10 Hz) elicited contraction and an overflow of tritium and ATP. Contractions as well as ATP overflow were reduced by prazosin 0.3 microM and even more so by prazosin 0.3 microM combined with suramin 300 microM. They were also reduced by nifedipine 10 microM and even more so by nifedipine 10 microM combined with ryanodine 20 microM (the additional effect of ryanodine on ATP overflow was not significant). In tissues not pretreated with [3H]-noradrenaline, exogenous noradrenaline 10 microM and alpha,beta-methylene ATP 10 microM elicited contraction and an overflow of ATP. Responses to noradrenaline were blocked by prazosin 0.3 microM but not suramin 300 microM and were greatly reduced by nifedipine 10 microM and in Ca(2+)-free medium. Responses to alpha,beta-methylene ATP were blocked by suramin 300 microM but not prazosin 0.3 microM, were reduced by nifedipine 10 microM (effect on ATP overflow not significant) and were reduced even more in Ca(2+)-free medium. Neuropeptide Y 0.3 microM caused only very small contraction and ATP overflow. The electrically as well as the agonist-evoked ATP overflow correlated well with the contraction responses except in experiments with suramin which retarded the removal, by vas deferens tissue, of ATP from the medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1994

Release-inhibiting alpha 2-adrenoceptors at serotonergic axons in rat and rabbit brain cortex: evidence for pharmacological identity with alpha 2-autoreceptors.

The pharmacological properties of the presynaptic alpha 2-adrenoceptors modulating the release of serotonin in rat and rabbit brain cortex (alpha 2-heteroreceptors) were compared with the properties of presynaptic alpha 2-autoreceptors in the same brain area. Brain cortex slices were preincubated with [3H]-serotonin or [3H]-noradrenaline and then superfused and stimulated by brief high-frequency pulse trains. The alpha 2-adrenoceptor agonist bromoxidine reduced the electrically evoked overflow of tritium in experiments with both [3H]-noradrenaline and [3H]-serotonin and in brain slices from either species. The antagonists phentolamine, idazoxan, (+)-mianserin, rauwolscine, 5-chloro-4-(1-butyl-1,2,5,6-tetrahydropyridin-3-yl)-thiazole-2-ami ne (ORG 20350), 2-(2,6-dimethoxyphenoxyethyl)amino-methyl-1,4-benzodioxane (WB 4101), (-)-mianserin and corynanthine caused parallel shifts of the concentration-inhibition curves of bromoxidine to the right. Negative logarithms of antagonist dissociation constants pKd were calculated from the shifts. In the rat, the alpha 2-autoreceptor pKd value of each single antagonist was similar to its alpha 2-heteroreceptor pKd value, maximal difference 0.4, giving a close correlation, r = 0.97 (P < 0.001). In the rabbit equally, the alpha 2-autoreceptor pKd value of each single antagonist was similar to its alpha 2-heteroreceptor pKd value, maximal difference 0.4, again yielding a close correlation, r = 0.96 (P < 0.001). However, antagonist pKd values at rat alpha 2-autoreceptors differed from those at rabbit alpha 2-autoreceptors, r = 0.70 (P > 0.05), and antagonist pKd values at rat alpha 2-heteroreceptors differed from those at rabbit alpha 2-heteroreceptors, r = 0.64 (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1994

P2-purinoceptor antagonists discriminate three contraction-mediating receptors for ATP in rat vas deferens.

The sites of action at which ATP elicits contraction of the rat vas deferens were studied by means of the P2-purinoceptor antagonists pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (iso-PPADS), suramin and reactive blue 2. Increasing concentrations of iso-PPADS (up to 1 mM), suramin (up to 1 mM) and reactive blue 2 (up to 320 microM) reduced and eventually abolished contractions elicited by the P2x-purinoceptor-selective agonist alpha,beta-methylene ATP 3 microM with IC50 values of 2.1, 10.1 and 27.0 microM, respectively. In contrast, iso-PPADS and suramin caused only a partial inhibition of contractions elicited by ATP 1 mM, maximal reduction by about 40%, IC50 values 1.3 and 5.0 microM, respectively; reactive blue 2 did not change ATP-induced contractions. In tissues exposed to iso-PPADS 320 microM throughout, increasing concentrations of reactive blue 2 or suramin decreased contractions elicited by ATP 1 mM, IC50 values 2.6 and 14.5 microM, respectively. In tissues exposed to suramin 320 microM throughout, increasing concentrations of iso-PPADS decreased contractions elicited by ATP 1 mM, IC50 37.9 microM, whereas reactive blue 2 slightly enhanced these contractions. In tissues exposed to reactive blue 2 100 microM throughout, increasing concentrations of iso-PPADS reduced contractions elicited by ATP 1 mM, IC50 26.6 microM, whereas suramin caused no change. Pre-exposure to alpha,beta-methylene ATP 1 microM to desensitize P2x-purinoceptors reduced the response to ATP 1 mM by 91% in otherwise untreated tissues, but did not reduce the response to ATP 1 mM in tissues exposed throughout to iso-PPADS 320 microM, suramin 320 microM or reactive blue 2 100 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1994

P1-purinoceptor-mediated modulation of neural noradrenaline and ATP release in guinea-pig vas deferens.

The effect of P1-purinoceptor activation on contractions, release of noradrenaline and release of ATP elicited by electrical field stimulation (210 pulses, 7 Hz) was studied in the superfused vas deferens of the guinea pig. Release of noradrenaline was assessed as overflow of total tritium after preincubation with [3H]-noradrenaline. ATP was measured by means of the luciferin-luciferase technique. Electrical stimulation elicited reproducible contraction, tritium overflow and ATP overflow. In the absence of other drugs, adenosine (10-100 microM) did not change evoked contractions but reduced the evoked overflow of tritium and ATP. In subsequent experiments alpha 1-adrenoceptors were blocked by prazosin, P2-purinoceptors by suramin and alpha 2-adrenoceptors by rauwolscine. No or almost no contraction remained under these conditions. The evoked overflow of tritium was 505% and the evoked overflow of ATP 34% of that observed in the absence of prazosin, suramin and rauwolscine. Adenosine (1-100 microM) again reduced the evoked overflow of tritium and ATP, and so did the A1-selective agonist 2-chloro-N6-cyclopentyladenosine (CCPA; 0.032-0.32 microM). Adenosine and CCPA decreased the evoked overflow of ATP to a greater extent than the evoked overflow of tritium. It is concluded that neural release of both postganglionic sympathetic cotransmitters, noradrenaline and ATP, is decreased upon activation of prejunctional P1- (A1-) purinoceptors in guinea-pig vas deferens. The A1-receptor-mediated inhibition of the release of ATP is more marked than the inhibition of the release of noradrenaline, a pattern opposite to the inhibition produced by activation of prejunctional alpha 2-autoreceptors.

Action Potentials↗
PubMed1994

Corelease of noradrenaline and ATP by brief pulse trains in guinea-pig vas deferens.

Contractions and overflow of tritium and ATP elicited by single electrical pulses or short pulse trains were studied in the guinea-pig isolated vas deferens preincubated with [3H]-noradrenaline. ATP was measured using the luciferase technique. A single pulse caused only a small contraction and minimal tritium and ATP overflow. In contrast, trains of 6 pulses elicited marked contractions as well as tritium and ATP overflow. In experiments with 6 pulses/100 Hz, prazosin 0.3 microM reduced the contraction by 73%, did not change the evoked overflow of tritium, and reduced the evoked overflow of ATP by 85%. Suramin 300 microM reduced the contraction by 69% but changed neither the evoked overflow of tritium nor that of ATP. The combination of prazosin 0.3 microM and suramin 300 microM abolished the contraction, did not change the evoked overflow of tritium, and reduced the evoked overflow of ATP by 70%. When 6 pulses were applied at frequencies of 1, 2, 10 or 100 Hz, all responses increased with frequency up to a maximum at 10 Hz, but contractions and the evoked overflow of ATP increased with frequency to a greater extent than the evoked overflow of tritium. A similar frequency overflow relationship was observed when the medium contained prazosin 0.3 microM and suramin 300 microM (and evoked ATP overflow was greatly reduced). Yohimbine 1 microM did not affect the overflow of tritium evoked by 6 pulses/100 Hz but increased that evoked by 6 pulses/10 Hz. The results demonstrate an overflow of both noradrenaline and ATP in response to short pulse trains.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1994

Co-release of noradrenaline and ATP from cultured sympathetic neurons.

The vesicles of postganglionic sympathetic axons store both noradrenaline and ATP. The theory of noradrenaline-ATP co-transmission implies that both compounds are released by nerve action potentials and elicit postjunctional effects. Many properties of postjunctional responses support the theory. However, neural release of ATP has been difficult to detect biochemically: by far the major part of the overflow of ATP from intact tissues upon sympathetic nerve stimulation comes from non-neural elements, especially smooth muscle and endothelial cells. Here we describe a parallel electrically evoked overflow of [3H]noradrenaline and endogenous ATP from cultured chick sympathetic neurons. The overflow was abolished by tetrodotoxin, omega-conotoxin and withdrawal of Ca2+, was increased by tetraethylammonium and 4-aminopyridine, and was not changed by prazosin or suramin. The results demonstrate directly the action potential-evoked, Ca(2+)-dependent and presumably vesicular and exocytotic release of ATP from postganglionic sympathetic neurons. They support the co-transmitter theory and suggest that cultured sympathetic neurons are a preparation in which noradrenaline-ATP co-release can be examined free from postjunctional components.

4-Aminopyridine↗
PubMed1994

Sexuality, sexual behaviour and contraception in East Germany.

Social factors may influence sexual health and its related behaviour. The political changes in East Germany have revealed a positive attitude towards sexuality and the use of family planning methods. A study on sexual behaviour and the use of contraceptives was undertaken recently, at the end of the old regime and the beginning of the new one. The survey was performed among 3103 male and female respondents (pupils, students and workers) of between 16 and 48 years of age. The results show a decreased number of stable partner relationships among young people, however, love and sexuality are considered to be central values. Before the age of 19 years, the majority of girls (80%) and boys (68%) had had sexual intercourse for the first time, a rate which has not changed during the last decade. There is a tendency to postpone having a first child. Modern contraception is widely accepted and used. There is a growing number of condom users, however, the pill is still the most popular method. Family planning is much more advanced than in the other countries of Eastern Europe. Sex education and counselling should sustain this situation.

Adolescent↗
PubMed1994

Presynaptic modulation of the release of the co-transmitters noradrenaline and ATP.

The release of both sympathetic co-transmitters, noradrenaline and ATP, is modulated via presynaptic receptors. However, the degree of the modulation may differ indicating that the ratio of the released co-transmitters changes upon presynaptic receptor activation. For example, alpha 2-autoinhibition affects the release of noradrenaline more markedly than the release of ATP. Some sympathetic axon terminals possess presynaptic P2-purinoceptors which are activated by endogenous ATP. These receptors are a novel kind of auto-receptor: they mediate a presynaptic negative feedback mechanism in which released ATP inhibits subsequent co-transmitter release.

Adenosine Triphosphate↗