Inhibition of adrenergic neurotransmission by clonidine: An action on prejunctional α-receptors

Starke, Klaus; Altmann, Karina

doi:10.1016/0028-3908(73)90093-2

Cited by 229 publications

(51 citation statements)

References 17 publications

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“…It has been suggested that activation by clonidine of presynaptic a-adrenoceptors in the central nervous system is causally related to its antihypertensive effects (Starke & Altman, 1973). Yet, Haeusler (1974) and Kobinger & Pichler (1976) demonstrated that clonidine and other imidazolines exert their sympathoinhibitory effects and thus hypotension and bradycardia, by stimulation of postsynaptic rather than presynaptic a-adrenoceptors in the central nervous system.…”

Section: A)mentioning

confidence: 99%

Sixth Gaddum Memorial Lecture National Institute for Medical Research, Mill Hill, January 1977

Langer

1977

British J Pharmacology

917

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Section: A)mentioning

confidence: 99%

Sixth Gaddum Memorial Lecture National Institute for Medical Research, Mill Hill, January 1977

Langer

1977

British J Pharmacology

917

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“…This observation provided one of the earliest arguments for the ac-feedback concept that went beyond the simple qualitative effects of agonists and antagonists (Starke, 1972;Starke & Altmann, 1973;Reichenbacher, Reimann & Starke, 1982). Competition between exogenous agonist and liberated noradrenaline for one set of autoreceptors may also explain in part the inverse relationship that exists between the inhibition caused by the exogenous agonist and the frequency of stimulation (Vizi, Somogyi, Hadhazy & Knoll, 1973;Starke, Montel, Gayk & Merker, 1974;Langer, Dubocovich & Celuch, 1975).…”

Section: Discussionmentioning

confidence: 96%

Release of [³H]‐amezinium from cortical noradrenergic axons: a model for the study of the α‐autoreceptor hypothesis

Hedler¹,

Starke²,

Steppeler³

1983

British J Pharmacology

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[3H]-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-a-adrenergic marker in order to study the a-adrenergic autoinhibition of noradrenaline release.2 Rat occipitocortical slices were preincubated with [3H]-amezinium 0.03 tLM 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 [3H]-amezinium; from saline-treated rats, slices from which were exposed simultaneously to noradrenaline and cocaine before preincubation with [3H]-amezinium; from rats in which noradrenaline stores had been depleted by pretreatment with a-methyltyrosine (a-NMT); from a-MT-treated rats, the slices being exposed to noradrenaline before preincubation with [3H]-amezinium; and from a-MT-treated rats, slices from which were exposed to noradrenaline plus cocaine before preincubation with [3H]-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 salinepretreated rats after exposure to noradrenaline or noradrenaline plus cocaine. It was 2.56 % in slices from a-MT-treated rats, 1.20% from a-MT-treated rats after exposure to noradrenaline, and 2.88% from a-MT-treated rats after exposure to noradrenaline plus cocaine. 4 Yohimbine 0.1 and 1 piM increased the stimulation-evoked overflow of tritium in slices from all groups of saline-pretreated rats and in those slices from a-MT rats that had been in contact with exogenous noradrenaline. Yohimbine did not change the evoked overflow in slices from a-MT rats that had not been exposed to noradrenaline, or had been exposed to noradrenaline plus cocaine. 5 Clonidine 0.01-1 LM decreased the stimulation-evoked overflow of tritium moderately in slices from saline-pretreated rats, markedly in slices from a-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 [3H]-amezinium as well as the modulation of this release by yohimbine and clonidine depend on the presence or absence of a-adrenergic autoinhibition caused by the co-secretion of noradrenaline. When there is co-secretion of noradrenaline, the evoked release of [3H]-amezinium is relatively small, yohimbine increases the release, and clonidine can cause only moderate inhibition. When there is no or very little cosecretion of noradrenaline, the evoked release of [3H]-amezinium is at least doubled, yohimbine causes no further increase and clonidine produces strong inhibition.

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“…lated atrium (Benfey & Greeff, 1961) and increased noradrenaline overflow in the rabbit isolated heart by inhibiting noradrenaline removal (Starke, Montel & Wagner, 1971). In the rabbit heart, cocaine (15 gM) did not inhibit the increase in noradrenaline caused by phentolamine (Starke et al,197 1) but reduced the decrease in noradrenaline release caused by clonidine (Starke & Altmann, 1973). Clonidine must compete with endogenous noradrenaline for presynaptic a-adrenoceptors, and cocaine increases the concentration of noradrenaline in the synaptic cleft by inhibiting its neuronal uptake.…”

Section: Introductionmentioning

confidence: 99%

“…We used a simple method for stimulating autonomic nerves and causing the release of transmitters: subjecting isolated heart muscle preparations to intense electrical stimulation (Blinks, 1966;Katz & Kopin, 1969). In the rabbit isolated heart the sympathomimetic drug, clonidine, antagonized the increase in the stimulation-induced release of noradrenaline caused by the a-adrenoceptor blocking drug, phentolamine (Starke & Altmann, 1973). In the guinea-pig left atrial strip clonidine reduced, and phentolamine increased, the positive inotropic response to intense electrical stimulation (Malta, Ong, Raper, Tawa & Vaughan, 1980).…”

Section: Introductionmentioning

confidence: 99%

Presynaptic Effect of Clonidine Antagonized by the Tetramine Disulphide, Benextramine

Belleau¹,

Benfey²,

Melchiorre³

1982

British J Pharmacology

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1 The presynaptic a-adrenoceptor blocking activity of the newly synthesized a-adrenoceptor blocking drug, benextramine, was evaluated in the isolated left atrium of the guinea-pig heart. 2 High-voltage stimulation increased the force of contraction of electrically driven atrial strips, presumably by releasing noradrenaline from sympathetic nerve endings. Like phentolamine, benextramine increased the effect of high-voltage stimulation, presumably by blocking presynaptic a-adrenoceptors. 3 Clonidine reduced the effect of high-voltage stimulation, presumably by stimulating presynaptic a-adrenoceptors. The inhibitory effect of clonidine was antagonized noncompetitively by benextramine and competitively by phentolamine. 4 Combined administration of benextramine and phentolamine only resulted in the competitive phentolamine antagonism. Thus phentolamine protected the presynaptic a-adrenoceptors against benextramine blockade.

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Inhibition of adrenergic neurotransmission by clonidine: An action on prejunctional α-receptors

Cited by 229 publications

References 17 publications

Sixth Gaddum Memorial Lecture National Institute for Medical Research, Mill Hill, January 1977

Sixth Gaddum Memorial Lecture National Institute for Medical Research, Mill Hill, January 1977

Release of [³H]‐amezinium from cortical noradrenergic axons: a model for the study of the α‐autoreceptor hypothesis

Presynaptic Effect of Clonidine Antagonized by the Tetramine Disulphide, Benextramine

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Inhibition of adrenergic neurotransmission by clonidine: An action on prejunctional α-receptors

Cited by 229 publications

References 17 publications

Sixth Gaddum Memorial Lecture National Institute for Medical Research, Mill Hill, January 1977

Sixth Gaddum Memorial Lecture National Institute for Medical Research, Mill Hill, January 1977

Release of [3H]‐amezinium from cortical noradrenergic axons: a model for the study of the α‐autoreceptor hypothesis

Presynaptic Effect of Clonidine Antagonized by the Tetramine Disulphide, Benextramine

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Release of [³H]‐amezinium from cortical noradrenergic axons: a model for the study of the α‐autoreceptor hypothesis