Studies on the Interactions of Guanethidine and Bretylium With Noradrenaline Stores

Chang, Cheng-Chieh; Chang, Jung‐Chen; Su, Chun-Han

doi:10.1111/j.1476-5381.1967.tb02127.x

Cited by 11 publications

(6 citation statements)

References 32 publications

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“…Nevertheless, the additional complicating factor of the onset of the stimulant effect of guanethidine at 10-5 M, which is due to an indirect sympathomimetic action (Gillespie & McGrath, 1975), suggests caution in interpreting the net effects of this agent. Furthermore, the motor nerves of the rat vas deferens are relatively resistant to blockade by guanethidine compared, for example, with vasopressor nerves (Chang, Chang & Su, 1967). Even with 10-4 M-guanethidine the response of the prostatic portion of rat vasa deferentia to repetitive stimulation was not abolished (Anton et al 1977), and in the present experiments a residual response remained to a single stimulus even after 10-4M-guanethidine and ac-adrenoceptor blockade, pointing to a type of neurotransmission which, unlike other examples of sympathetic transmission, is attenuated by guanethidine, but not abolished by it.…”

Section: Discussionmentioning

confidence: 99%

Adrenergic and 'non‐adrenergic' components in the contractile response of the vas deferens to a single indirect stimulus.

McGrath¹

1978

The Journal of Physiology

220

155

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SUMMARY1. The mechanical response of the longitudinal smooth muscle of the rat vas deferens to stimulation of its motor nerves by a single pulse has been examined. The motor nerves were stimulated in vivo via the spinal outflows in the pithed rat or in vitro by field stimulation.2. The contraction in the whole vas consisted of two components, an initial, rapid, brief contraction reaching a maximum at 300 msec and a second, slower and more prolonged contraction reaching its maximum at 600 msec. When the isolated vas was divided into prostatic and epididymal halves the contribution of these two components varied. The initial rapid component was more prominent in the prostatic half and the slower, second component more prominent in the epididymal half. Lowering the bath temperature caused, in both halves, these two components to merge into a single, slow, prolonged response. Both components were more rapid and briefer than the equivalent response of rat anococcygeus.3. The second, slow component was abolished by a-adrenoceptor antagonist drugs, potentiated and prolonged by drugs which inhibit the neuronal uptake of noradrenaline and absent from tissues taken from rats pre-treated with reserpine, suggesting that the neurotransmitter for this component is noradrenaline.4. These experiments were extended to the mouse or guinea-pig vas deferens. Both showed the same two component mechanical response as the rat vas and in both the second, slow component was preferentially inhibited by x-adrenoceptor antagonists and potentiated by drugs blocking noradrenaline uptake.5. Drugs known to reduce the response to repetitive nerve stimulation of the vas were examined for their effect on the response to a single stimulus. Lysergic acid diethylamide preferentially inhibited the second, slow phase of contraction whereas apomorphine preferentially inhibited the first rapid phase. Guanethidine inhibited responses but any differential effects could not be analysed due to its stimulant properties.6. These results show that there are two components even to the response to a single stimulus. The second of these appears to be adrenergic while the transmitter responsible for the first remains to be determined.

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Section: Discussionmentioning

confidence: 99%

Adrenergic and 'non‐adrenergic' components in the contractile response of the vas deferens to a single indirect stimulus.

McGrath¹

1978

The Journal of Physiology

220

155

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“…In an earlier study in anaesthetized rats, Chang, Chang & Su (1967) measured the intraluminal pressure in a blind sac of vas deferens as described by Langley & Anderson (1895) and found only one component to the response during hypogastric nerve stimulation. Evidently this latter preparation also did not respond rapidly enough to detect the twitch component.…”

Section: Measurement Of Responsesmentioning

confidence: 99%

An analysis of the anatomical basis for the mechanical response to motor nerve stimulation of the rat vas deferens

Anton¹,

Duncan²,

McGrath³

1977

The Journal of Physiology

100

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1. An anatomical basis was sought for the biphasic motor nerve response of the rat vas deferens. The motor nerve pathway to the tissue was stimulated at different points between the vertebral outflow and the intramural fibres, in the pithed rat and in isolated tissues, to examine the possibility of two anatomically separate groups of neurones. Different preparations of the isolated tissue were devised to detect whether different groups of smooth muscle fibres contributed to the two phases. 2. The fibres mediating both phases of the response arose from the upper lumbar vertebral outflows. Both phases were elicited by pre‐ or post‐ganglionic stimulation and could be depressed by hexamethonium. In the pithed rat or with hypogastric nerve stimulation in the isolated tissue, however, the initial ‘twitch’ phase was relatively resistant to such blockade. 3. When the rat vas deferens was perfused through the lumen in situ or in vitro, the perfusion pressure response to motor nerve stimulation exhibited two phases similar to those of the longitudinal contractile response. 4. Isolated rat vasa were bisected into portions, each of which was stimulated and longitudinal tension was recorded. The proportions of the two phases of the response varied along the length of the tissue. At the prostatic end the total response was relatively weak with a dominant ‘twitch’ and at the epididymal end the two phases were comparable in magnitude. The distribution of adrenergic nerve terminals within the muscle layers also varied along the length of the rat vas deferens. 5. The effects of drugs were investigated on the motor responses of the above preparations. The ‘twitch’ phase was relatively susceptible to blockade by reserpine and lysergic acid diethylamide and the ‘secondary’ phase to phentolamine with both equally sensitive to guanethidine. Each phase had similar susceptibilities to blockade irrespective of which part of the tissue was involved. 6. It was concluded that two types of nerve‐muscle transmission may be involved in the rat vas deferens with the proportion of each varying along the length of the tissue but both displaying pharmacological characteristics of adrenergic fibres.

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“…The exception to this generalization was provided by Cession-Fossion (1965) who showed that bretylium initially produced an increase and later a decrease in the noradrenaline content of rat heart. *Present address: Department of Pharmacology, Karolinska Institutet, Stockholm 60, Sweden. Bretylium had also been shown to have no effect on the subcellular distribution of noradrenaline (Chang et al, 1967).…”

Section: Introductionmentioning

confidence: 99%

“…Many of the original studies on the acute effects of bretylium indicated that this drug had no effect on the tissue content of noradrenaline at a time when adrenergic neurone blockade was evident (Brodie & Kuntzman, 1960;Cass & Spriggs, 1961;Bhagat & Shideman, 1963;Bhagat & Gilliam, 1965;Spriggs, 1966;Chang, Chang & Su, 1967; Krauss, Kopin & Weise, 1970). The exception to this generalization was provided by Cession-Fossion (1965) who showed that bretylium initially produced an increase and later a decrease in the noradrenaline content of rat heart.…”

Section: Introductionmentioning

confidence: 99%

The effects of bretylium on the subcellular distribution of noradrenaline and on adrenergic nerve function in rat heart

Abbs

Pycock

1973

British J Pharmacology

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Summary1. The effects of bretylium were investigated on the content and subcellular distribution of noradrenaline in the rat heart and on the response to stimulation of the sympathetic nerves supplying the heart. 2. In most experiments bretylium produced no change in the total noradrenaline content of the heart but significant changes were produced in the subcellular distribution of noradrenaline. 3. Treatment with amphetamine both prevented and antagonized the bretylium-induced adrenergic neurone blockade and most of the accompanying changes in the subcellular distribution of noradrenaline. 4. There was a temporal correlation between the bretylium-induced depletion of noradrenaline from the microsomal (P2) fraction and adrenergic neurone blockade. 5. The onset of adrenergic neurone blockade was also accompanied by an elevation of the noradrenaline content in the low-speed coarse (PWA) fraction and in the mitochondrial (P1.) fraction; this elevation was prevented by pretreatment with a-methyl-p-tyrosine. 6. It is concluded that although the elevation of the noradrenaline content of the P1A and P,B fractions and a depletion of amine from the P2 fraction are associated with the onset of adrenergic neurone blockade only the depletion from the P2 fraction is required for its maintenance. This conclusion supports the hypothesis that only a small portion of the noradrenaline content of an adrenergically-innervated organ is associated with the release of transmitter, for when this small 'store' is depleted, by agents like bretylium, the nerves fail to function.

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Studies on the Interactions of Guanethidine and Bretylium With Noradrenaline Stores

Cited by 11 publications

References 32 publications

Adrenergic and 'non‐adrenergic' components in the contractile response of the vas deferens to a single indirect stimulus.

Adrenergic and 'non‐adrenergic' components in the contractile response of the vas deferens to a single indirect stimulus.

An analysis of the anatomical basis for the mechanical response to motor nerve stimulation of the rat vas deferens

The effects of bretylium on the subcellular distribution of noradrenaline and on adrenergic nerve function in rat heart

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