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K Starke

Publications and source records attributed to K Starke.

At least 199 records · Page 11Linked to original sources
PubMed1985

Presynaptic opioid receptor subtypes in the rabbit ear artery.

In segments of rabbit ear arteries preincubated with [3H]noradrenaline, Leu-enkephalin, D-Ala2-D-Leu-enkephalin and ethylketocyclazocine concentration dependently reduced the overflow of tritium and the vasoconstriction elicited by field stimulation (120 pulses every 14 min, 1 Hz, 0.3 msec pulse duration). The effects of Leu-enkephalin and ethylketocyclazocine were antagonized by naloxone which, given alone, increased the evoked overflow of tritium at the high concentration of 10 microM. Morphine failed to produce inhibition, and at 100 microM actually increased evoked 3H-overflow. Continued exposure to Leu-enkephalin desensitized the tissue to this opioid; there was no cross-desensitization to ethylketocyclazocine. In arteries not preincubated with [3H]noradrenaline, normorphine, fentanyl and morphiceptin did not change the vasoconstrictor response (5 pulses every min, 5 Hz, 0.3 msec pulse duration). Among various peptide agonists, Leu-enkephalin, D-Ala2-D-Leu-enkephalin and Met-enkephalin were the most potent inhibitors. In a series of peptides with C-terminal extensions of the Met-enkephalin chain, the potency decreased in the order Met-enkephalin greater than Met-enkephalin-Arg-Gly-Leu greater than Met-enkephalin-Arg-Phe greater than BAM-12P greater than beta-endorphin. In a series of peptides with C-terminal extensions of the Leu-enkephalin chain, the potency decreased in the order Leu-enkephalin greater than dynorphin1-13 greater than dynorphin1-9 greater than alpha-neo-endorphin greater than dynorphin1-8 greater than dynorphin1-6 greater than dynorphin1-17. The delta-selective antagonist ICI 154129 counteracted the effect of Met-enkephalin but not that of dynorphin1-13, whereas naloxone counteracted the effect of either agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Neuronal and postjunctional components in the blood pressure effects of dopamine and bromocriptine in rabbits.

We have studied the contribution of neuronal and postjunctional dopamine (DA) receptors and of the DA1 and DA2 receptor subtypes to the blood pressure effects of DA and bromocriptine in the rabbit. The norepinephrine release rate, i.e., the rate of entry of endogenous norepinephrine into the plasma, was derived from the plasma level of endogenous norepinephrine and the plasma [3H]norepinephrine clearance. Bromocriptine (40 micrograms kg-1) lowered the norepinephrine release rate and the arterial blood pressure both in anesthetized rabbits and in pithed rabbits with electrically stimulated sympathetic outflow. These effects were antagonized by the selective DA2 antagonist domperidone but not by the selective DA1 antagonist SCH 23390. DA (10-160 micrograms kg-1 min-1) dose-dependently increased the norepinephrine release rate and caused only transient hypotension in anesthetized rabbits. However, after treatment with desipramine, DA did not change the norepinephrine release rate and produced a persistent fall in blood pressure. When DA and domperidone were given simultaneously to desipramine-treated rabbits, the hypotensive effect of DA was unchanged, but now DA increased the norepinephrine release rate. When DA and SCH 23390 were given simultaneously to desipramine-treated rabbits, DA failed to lower blood pressure and decreased the norepinephrine release rate. Propranolol did not change the effects of DA in desipramine-treated rabbits. These results suggest that bromocriptine decreases blood pressure by activating ganglionic and/or prejunctional, inhibitory DA2 receptors in the peripheral sympathetic nervous system. DA also activates these receptors, but in addition releases norepinephrine in the manner of an indirectly acting sympathomimetic amine and activates postjunctional vascular DA1 receptors, and the latter seems to be the main component in DA-induced hypotension.

Anesthesia↗
PubMed1984

Further study of prerequisites for the enhancement by alpha-adrenoceptor antagonists of the release of noradrenaline.

Segments of the rabbit ear artery were preincubated with (-)-3H-noradrenaline and then perfused/superfused and stimulated by transmural electrical pulses. The outflow of 3H-noradrenaline and total tritium was determined. In the first series of experiments, stimulation periods of approximately constant length (50 s) were used (cocaine 5 microM present). Thirteen pulses (0.25 Hz) elicited an overflow of 3H-noradrenaline of 0.024% of tissue tritium; 26 pulses (0.5 Hz) elicited an overflow of 0.059%, and 52 pulses (1 Hz) of 0.166%. Rauwolscine 1 microM did not change the overflow evoked by 13 pulses, increased that evoked by 26 pulses and increased most markedly that evoked by 52 pulses. Phentolamine 1 microM decreased the overflow at 13, did not change the overflow at 26, and increased the overflow at 52 pulses. Corynanthine 1 microM decreased the overflow at 13, and did not change the overflow at 26 and 52 pulses. The effect of tetraethylammonium (TEA) 100 microM was opposite to that of rauwolscine; it increased most markedly the overflow evoked by 13 pulses, increased less that evoked by 26 pulses, and least the overflow at 52 pulses. In the second series of experiments, the frequency of stimulation was kept constant (2 Hz). In the absence of cocaine, 10 pulses elicited an overflow of 3H-noradrenaline of 0.023% of tissue tritium; 20 pulses elicited an overflow of 0.043%, and 40 pulses of 0.089%. Phentolamine 1 microM did not change the overflow evoked by 10 pulses, increased that evoked by 20 pulses, and increased most markedly that evoked by 40 pulses.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1984

Ethylketocyclazocine decreases noradrenaline release and blood pressure in the rabbit at a peripheral opioid receptor.

Rabbits were pithed and their sympathetic outflow was stimulated electrically via the pithing rod. Arterial blood pressure, heart rate, the endogenous plasma noradrenaline level, the plasma 3H-noradrenaline clearance and the noradrenaline release rate (the rate of entry of endogenous noradrenaline into the plasma) were determined. Ethylketocyclazocine 0.1 mg kg-1 + 0.02 mg kg-1 h-1 and 1 mg kg-1 + 0.2 mg kg-1 h-1 but not 0.01 mg kg-1 + 0.002 mg kg-1 h-1 decreased blood pressure, the endogenous plasma noradrenaline level and the noradrenaline release rate. The effects of ethylketocyclazocine 1 mg kg-1 + 0.2 mg kg-1 h-1 were antagonized by naloxone 1 mg kg-1 + 0.5 mg kg-1 h-1. Given alone, naloxone caused no change. It is concluded that ethylketocyclazocine inhibits action potential-evoked release of noradrenaline from postganglionic sympathetic neurones, and hence can lower blood pressure, by a peripheral effect, possibly mediated by opioid receptors at the terminal axons.

Animals↗
PubMed1984

Effects of verapamil, diltiazem and ryosidine on the release of dopamine and acetylcholine in rabbit caudate nucleus slices.

Slices of the rabbit caudate nucleus were preincubated with 3H-dopamine or 3H-choline and then superfused with label-free medium. Release of 3H-dopamine and 3H-acetylcholine was elicited by either electrical stimulation at 8 (in one series 2) Hz, or an increase in the K+ concentration by 50 mmol/l, or addition of L-glutamate 1 mmol/l. Verapamil 1 mumol/l, diltiazem 1 and 10 mumol/l, and ryosidine 1 mumol/l failed to the reduce the electrically-, K+- and glutamate-evoked overflow of tritium. Verapamil 1 mumol/l and diltiazem 10 mumol/l also failed to reduce the electrically-evoked overflow (2 Hz) when dopamine receptors, neuronal dopamine uptake, and neuronal choline uptake were blocked by domperidone, nomifensine and hemicholinium, respectively. Inhibition of the evoked overflow of tritium was only obtained when concentrations were increased to verapamil 10 mumol/l, diltiazem 100 mumol/l and ryosidine 10 mumol/l. The inhibition was generally small. It was more evident for slices preincubated with 3H-choline than for those preincubated with 3H-dopamine, because in the latter verapamil, diltiazem and (much less) ryosidine accelerated the basal efflux of tritium. The inhibition of the K+-evoked overflow of tritium was probably due to blockade of Ca2+ channels because this overflow was Ca2+-dependent but tetrodotoxin-resistant. In contrast, the inhibition of the electrically- and glutamate-evoked overflow possibly involved blockade of Na+ channels as well. The results indicate that three calcium antagonists from different chemical classes are very weak inhibitors of Ca2+ entry into, and hence transmitter release from, the terminal axons of central dopaminergic and cholinergic neurones. The function of the high affinity calcium antagonist binding sites that have been identified in brain remains unknown.

Acetylcholine↗
PubMed1984

Forskolin and the release of noradrenaline in cerebrocortical slices.

The role of adenosine 3',5'-cyclic monophosphate (cAMP) in the release of noradrenaline from central neurones has been investigated by examining the effects of forskolin, 3-isobutyl-l-methylxanthine (IBMX), cis-6-(p-acetamidophenyl)-1,2,3,4,4a, 10b-hexahydro-8,9-dimethoxy-2-methyl-benzo[c] [1,6]-naphthyridine bis (+ +hydrogenmaleinate) (AH21-132; a new phosphodiesterase inhibitor) and N6,O2'-dibutyryl-adenosine 3',5'-cyclic monophosphate (dibutyryl-cAMP) on the outflow of tritiated compounds from rat and rabbit cerebral cortex slices preincubated with [3H]-noradrenaline. Forskolin, IBMX, AH21-132 and dibutyryl-cAMP produced a concentration-dependent increase in both basal and electrically-evoked efflux of tritium from rat and rabbit cortex slices. The increase in basal tritium efflux from rabbit cortex slices elicited by forskolin and IBMX could be attributed mainly to an increase in [3H]-DOPEG although a small increase in [3H]-noradrenaline was also observed. Forskolin and (when combined with noradrenaline) IBMX and AH21-132 increased the cAMP content of rat cortex slices at similar or somewhat higher concentrations that they increased tritium efflux. Neither forskolin nor IBMX or AH21-132 had any effect on the cocaine-sensitive uptake of [3H]-noradrenaline into synaptosomes prepared from rat or rabbit cortex. The effects of forskolin, IBMX and dibutyryl-cAMP on electrically-evoked overflow of tritium from rat and rabbit cortex slices were reduced when cocaine (10 microM) was present in the superfusion medium, although forskolin produced a similar increase in cAMP in the absence or presence of cocaine. It is suggested that cAMP may facilitate the normal process of noradrenaline release by nerve stimulation.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Inhibition via opioid mu- and delta-receptors of vagal transmission in rabbit isolated heart.

The nervi vagi of isolated perfused rabbit hearts were stimulated by 10 s trains of electrical pulses at 1, 2 or 5 Hz. Morphine, Met-enkephalin and D-Ala2,D-Leu5-enkephalin reduced the ensuing bradycardia with IC50 values of 148, 25 and 3.2 nM, respectively. Naloxone antagonized the effects of morphine and Met-enkephalin; KB values (dissociation constants of antagonist-receptor complex) were 1.1 and 33 nM, respectively. The delta-receptor-selective antagonist ICI 174864 antagonized Met-enkephalin, KB 28 nM, but at 0.2 microM did not antagonize morphine. It is concluded that vagal transmission to the rabbit heart can be inhibited by activation of both opioid mu- und delta-receptors.

Acetylcholine↗
PubMed1984

Tetrodotoxin-resistant release of 3H-noradrenaline from the mouse vas deferens by high intensity electrical stimulation.

Vasa deferentia of mice were preincubated with 3H-noradrenaline and then superfused with a medium containing cocaine 10 microM and phentolamine 30 microM. The tetrodotoxin-resistant outflow of tritium evoked by high intensity electrical field stimulation (0.5 Hz, 200 mA current strength, 2 ms pulse width) was studied and, in some experiments, compared with the tetrodotoxin-sensitive outflow evoked by low intensity electrical field stimulation (0.5 Hz, 50 mA, 1 ms). In contrast to the outflow evoked by low intensity stimulation, the outflow evoked by high intensity stimulation was increased in Na+-free medium, and was only partly dependent on the external Ca2+ concentration. The Ca2+-dependent fraction consisted mainly of 3H-noradrenaline. Again, in contrast to the outflow caused by stimulation at low intensity, that caused by stimulation at high intensity was not reduced by Mg2+ 20 mM, Co2+ 5 mM or normorphine 40 or 100 microM, and was not enhanced by tetraethylammonium 5 mM or 4-aminopyridine 1 mM. It is concluded that high intensity electrical stimulation elicits a tetrodotoxin-resistant, calcium-dependent release of noradrenaline which differs in mechanism from the release elicited by action potentials.

4-Aminopyridine↗
PubMed1983

Modulation of noradrenaline release in the conscious rabbit through alpha-adrenoceptors.

The effects of selective alpha 1- and alpha 2-adrenoceptor antagonists and agonists on the noradrenaline release rate and plasma catecholamine levels were studied in the conscious rabbit. The selective alpha 2-adrenoceptor blocking drugs yohimbine and rauwolscine (1 mg/kg i.v.) increased the rate of noradrenaline release into the plasma and the plasma noradrenaline and adrenaline levels. This was associated with a rise in blood pressure. The selective alpha 1-blocking drug corynanthine (1 mg/kg i.v.) had no effect. Intravenous infusions of the selective alpha 2-adrenoceptor agonist alpha-methylnoradrenaline (2 micrograms/kg per min) and the alpha 1-agonist phenylephrine (6 micrograms/kg per min) produced equipressor responses. However, only alpha-methylnoradrenaline decreased the noradrenaline release rate and the plasma noradrenaline and adrenaline levels, effects which were blocked by yohimbine. The results are compatible with, but of course do not prove the hypothesis that in the conscious rabbit, noradrenaline release from sympathetic nerves is modulated through presynaptic alpha 2-adrenoceptors. Adrenaline release from the adrenal medulla may also be subject to alpha 2-adrenergic modulation.

Adrenergic alpha-Agonists↗
PubMed1983

Evidence for a physiological role of presynaptic alpha-adrenoceptors: modulation of noradrenaline release in the pithed rabbit.

Rabbits were pithed and the preganglionic nerves at T 8 were stimulated continuously at a frequency of 3 Hz. 3H-noradrenaline was infused to reach a steady-state plasma level, from which the noradrenaline plasma clearance was calculated. The plasma level of endogenous noradrenaline was also determined and the rate of noradrenaline release into the plasma was then derived. The noradrenaline plasma clearance was decreased by guanethidine (7.5 mg/kg), desipramine (1 mg/kg), yohimbine (1 mg/kg) and rauwolscine (1 mg/kg). It was unaffected by corynanthine (1 mg/kg), prazosin (0.1 mg/kg), alpha-methylnoradrenaline (2 micrograms/kg per min) and clonidine (1 micrograms/kg per min). The electrical stimulation resulted in an increase in blood pressure without an increase in heart rate. Both adrenaline and noradrenaline were detected in the plasma. It is likely that the noradrenaline was of neuronal origin as guanethidine decreased its plasma level. The alpha 2-adrenoceptor-selective blocking drugs yohimbine and rauwolscine increased the noradrenaline release rate and only slightly decreased blood pressure. On the other hand, the alpha 1-adrenoceptor-selective blocking drugs corynanthine and prazosin had no effect on the noradrenaline release rate and decreased blood pressure more markedly. The alpha 2-adrenoceptor-selective agonists alpha-methylnoradrenaline and clonidine both decreased the noradrenaline release rate. This effect was blocked by yohimbine, and for the case of clonidine, not blocked by corynanthine. Plasma adrenaline levels were increased by yohimbine and rauwolscine, but not by corynanthine and prazosin. Clonidine reduced the plasma adrenaline level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1983

Further functional in vitro comparison of pre- and postsynaptic dopamine receptors in the rabbit caudate nucleus.

Slices of the rabbit caudate nucleus were preincubated with 3H-dopamine or 3H-choline and then superfused and stimulated electrically. DiPr-5,6-ADTN reduced the stimulation-evoked overflow of tritium over the same concentration range, independently of whether slices had been preincubated with 3H-dopamine or 3H-choline, and the same was true for apomorphine, NPA and pergolide. Three other putative dopamine receptor agonists, namely 3-PPP, DPI and SKF 38393, failed to decrease the evoked overflow of tritium. Each of six antagonists--(-)-sulpiride, (+)-sulpiride, CGP 11109 A, cis-flupentixol, domperidone and corynanthine--increased the evoked overflow over the same concentration range in experiments with 3H-dopamine and in those with 3H-choline. For each of these antagonists except cis-flupentixol, and also for chlorpromazine, haloperidol and rauwolscine, the pA2 values against apomorphine obtained in 3H-dopamine and in 3H-choline experiments were closely similar. The antagonist effect of cis-flupentixol against apomorphine was not purely competitive. (-)-Sulpiride was a more potent antagonist than (+)-sulpiride, and cis-flupentixol was more potent than trans-flupentixol. This study supplements a previous one in which (+/-)-sulpiride, metoclopramide and molindone were used as antagonists. It is a functional in vitro approach to receptor characterization, as opposed to radioligand binding studies or in vivo investigations. The results show that a large number of dopamine receptor agonists and 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.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1983

Partial agonist effect of 2-[2-(1,4-benzodioxanyl)]-2-imidazoline (RX 781 094) at presynaptic alpha 2-adrenoceptors in rabbit ear artery.

Ear arteries from rabbits were preincubated with 3H-noradrenaline and then perfused. 2-[2-(1,4-Benzodioxanyl)]-2-imidazoline (RX 781094) 0.1 or 1 microM reduced the overflow of 3H-noradrenaline and total tritium elicited by 13 electrical pulses at 0.25 Hz or 26 Pulses at 0.5 Hz. RX 781 094 1 microM increased the overflow elicited by 52 pulses at 1 Hz. The inhibitory effects were blocked by yohimbine 10 microM but not by prazosin 1 microM. The alleged antagonist RX 781 094 possesses intrinsic activity at the presynaptic alpha 2-autoreceptors of the ear artery.

Adrenergic alpha-Antagonists↗
PubMed1983

Presynaptic opioid receptors in the rabbit ear artery.

The effect of opioids was compared on field stimulation-induced 3H-noradrenaline overflow and vasoconstriction in the rabbit ear artery. Subtype-selective opioids were used, namely the mu-receptor agonist morphine, the delta-receptor agonist Leu-enkephalin and the kappa-receptor agonists ethylketocyclazocine and dynorphin1-13. Morphine (10 and 100 microM) exerted no inhibitory effect. The delta- and kappa-agonists depressed both the stimulation-evoked overflow and the vasoconstrictor responses with a similar potency. Naloxone prevented the effect of the respective agonists and in the same concentration range (3-10 microM) slightly increased transmitter release. During a continuous exposure of the preparation to Leu-enkephalin (0.1 microM) specific desensitization developed towards a higher concentration of this neuropeptide (1 microM), whereas the inhibition produced by ethylketocyclazocine (1 x microM) was unaffected. Exogenous and endogenous opioids may modulate transmitter release and in consequence vasoconstriction in the rabbit ear artery by acting on neuronal delta- and kappa-receptors.

Animals↗
PubMed1983

Experimental conditions required for the enhancement by alpha-adrenoceptor antagonists of noradrenaline release in the rabbit ear artery.

1 Segments of the rabbit ear artery were preincubated with (-)-[3H]-noradrenaline and then perfused/superfused and stimulated by transmural electrical pulses. The outflow of [3H]-noradrenaline, separated from its metabolites by column chromatography, was determined. 2 Tetrodotoxin abolished, cocaine increased, and clonidine reduced the overflow of [3H]-noradrenaline elicited by 10 shocks at 0.2 Hz, 10 shocks at 2 Hz or 100 shocks at 2 Hz. 3 The effects of yohimbine (0.1 or 1 microM), phentolamine (1 microM) and piperoxan (1 or 10 microM) depended on the stimulation conditions. No antagonist increased the overflow of [3H]-noradrenaline evoked by 10 pulses at 0.2 Hz, but all markedly increased the overflow evoked by 100 pulses at 2 Hz. Only piperoxan (10 microM) slightly enhanced the overflow at 10 pulses, 2 Hz. The effects of yohimbine and piperoxan were similar in arteries not exposed to cocaine and in those that were perfused/superfused with medium containing cocaine (10 microM) after preincubation. 4 It is concluded that yohimbine, phentolamine and piperoxan increase the release of noradrenaline only when the concentration of noradrenaline in the biophase of the ear artery is sufficiently high. The effect is, hence, an anti-noradrenaline effect and due to the blockade of presynaptic alpha-adrenoceptors. A second prerequisite for the release-enhancing effect appears to be a sufficient length of the pulse train, indicating that the alpha-adrenergic auto-inhibition develops relatively slowly.

Adrenergic alpha-Antagonists↗
PubMed1983

An electrophysiological study of presynaptic alpha-adrenoceptors in the vas deferens of the mouse.

1--Effects of clonidine and alpha-adrenoceptor antagonists were studied on sympathetic neuroeffector transmission in the mouse vas deferens. The amplitude of excitatory junction potentials (e.j.ps) was taken as a measure of transmitter release per impulse. 2--At a concentration of 0.5 microM, prazosin abolished depolarizations evoked by iontophoretically applied noradrenaline, but changed neither spontaneous nor nerve stimulation-evoked e.j.ps. 3--Yohimbine 0.1 and 1 microM, rauwolscine 1 microM and corynanthine 1 microM di not change the e.j.p. amplitudes elicited by the first 2-3 pulses in trains of 15 pulses at 3 Hz, but increased the e.j.ps elicited by the subsequent pulses. Corynanthine 1 microM was much less effective than yohimbine 1 microM or rauwolscine 1 microM, and corynanthine 0.1 microM had no effect. 4--Clonidine 0.01 microM reduced the e.j.p. amplitudes evoked by single pulses and its effect was counteracted by yohimbine 1 microM. 5--In vasa deferentia from reserpine-treated mice the e.j.p. trains were changed in much the same way as by yohimbine and rauwolscine. Yohimbine 1 microM did not further increase the e.j.p. amplitudes in these organs, whereas clonidine 0.01 microM caused a marked inhibition. 6--It is concluded that the release of the motor transmitter in the mouse vas deferens is inhibited by activation of presynaptic alpha-adrenoceptors, and that these receptors are normally activated by neurally released noradrenaline.

Animals↗
PubMed1983

Release of [3H]-amezinium from cortical noradrenergic axons: a model for the study of the alpha-autoreceptor hypothesis.

1 [(3)H]-amezinium is taken up selectively into noradrenergic axons and their transmitter-storing vesicles and is released from these axons by action potentials. We used it as a non-alpha-adrenergic marker in order to study the alpha-adrenergic autoinhibition of noradrenaline release.2 Rat occipitocortical slices were preincubated with [(3)H]-amezinium 0.03 muM and then superfused and stimulated electrically (3 Hz for 3 min). The stimulation-evoked overflow of tritium was measured in six groups of slices: from saline-pretreated rats; from saline-pretreated rats, the slices being exposed to exogenous noradrenaline before preincubation with [(3)H]-amezinium; from saline-treated rats, slices from which were exposed simultaneously to noradrenaline and cocaine before preincubation with [(3)H]-amezinium; from rats in which noradrenaline stores had been depleted by pretreatment with alpha-methyltyrosine (alpha-MT); from alpha-MT-treated rats, the slices being exposed to noradrenaline before preincubation with [(3)H]-amezinium; and from alpha-MT-treated rats, slices from which were exposed to noradrenaline plus cocaine before preincubation with [(3)H]-amezinium.3 The stimulation-evoked overflow of tritium, expressed as a percentage of the tritium content of the tissue, was 1.15% in slices from saline-pretreated rats, and was similar in slices from saline-pretreated rats after exposure to noradrenaline or noradrenaline plus cocaine. It was 2.56% in slices from alpha-MT-treated rats, 1.20% from alpha-MT-treated rats after exposure to noradrenaline, and 2.88% from alpha-MT-treated rats after exposure to noradrenaline plus cocaine.4 Yohimbine 0.1 and 1 muM increased the stimulation-evoked overflow of tritium in slices from all groups of saline-pretreated rats and in those slices from alpha-MT rats that had been in contact with exogenous noradrenaline. Yohimbine did not change the evoked overflow in slices from alpha-MT rats that had not been exposed to noradrenaline, or had been exposed to noradrenaline plus cocaine.5 Clonidine 0.01-1 muM decreased the stimulation-evoked overflow of tritium moderately in slices from saline-pretreated rats, markedly in slices from alpha-MT-treated rats, and moderately again when the latter slices had been exposed to noradrenaline.6 It is concluded that the action potential-evoked release of [(3)H]-amezinium as well as the modulation of this release by yohimbine and clonidine depend on the presence or absence of alpha-adrenergic autoinhibition caused by the co-secretion of noradrenaline. When there is co-secretion of noradrenaline, the evoked release of [(3)H]-amezinium is relatively small, yohimbine increases the release, and clonidine can cause only moderate inhibition. When there is no or very little co-secretion of noradrenaline, the evoked release of [(3)H]-amezinium is at least doubled, yohimbine causes no further increase and clonidine produces strong inhibition.

Animals↗