The Selective Accumulation of Bretylium in Sympathetic Ganglia and Their Postganglionic Nerves

Boura, A. L. A.; Copp, F. C.; Duncombe, W. G.; Green, A. F.; McCoubrey, A.

doi:10.1111/j.1476-5381.1960.tb01242.x

Cited by 61 publications

(52 citation statements)

References 7 publications

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“…In the same line Boura et al (2) and Bentley (3) have shown that the response is abolished by the addition of reserpine, guanethidine and bretylium. The enhancement of the response by the addition of carbamyl-choline has been shown by Bentley.…”

supporting

confidence: 54%

Effects of Ganglionic Blocking Agents on Responses of Ductus Deferens Preparation of Guinea-Pig to Hypogastric Nerve Stimulation

Yamamoto

Nakanishi

1964

Japanese Journal of Pharmacology

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The sympathetic nature of the hypogastric innervation of the ductus deferens of guinea-pig has been concluded by Hukovic (1) from the results that the contractile response of the isolated ductus deferens to stimulation of the hypogastric nerve is en hanced by the addition of noradrenaline and is abolished by the previous reserpiniza tion of the animal. In the same line Boura et al. (2) (5) have demonstrated the enhancement of the response by the addition of eserine and various adrenolytics. The potentiating effect of the adrenolytics has been explained by the anticholinesterase activity of the drugs. The transmission failure of the sympathetic nerve impulse in the preparation by hemi cholinium has been shown by Chang and Rand (6) and Bentley (3). The inhibition of the contractile response by the ganglionic blocking agents has been shown by Sjostrand (7) and Bentley (3). Sjostrand (8) has proved that the chronic denervation of the ductus deferens does not affect the level of noradrenaline in the tissue. He has further indi cated that the cholinergic mechanism of impulse transmission in the preparation is responsible for the release of the endogenous noradrenaline.The assumption that the peripheral cholinergic mechanism is involved in the sym pathetic innervation of the ductus deferens of guinea-pig facilitated the current studies. METHODSSympathetically innervated ductus deferens preparation : Male guinea-pig, weighing 250 to 500 g, was killed by a blow on the head. The ductus deferens attached with hypo gastric nerve were prepared following the method devised by Hukovic (1).The preparation was tied by its proximal end to a hollow glass rod and by its distal end to a lever. It was set up in isolated organ-bath containing 50 ml of Kreb's solution at 31`C bubbled with 100% of oxygen. The contractile movement of the pre paration was recorded on the smoked drum.

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confidence: 54%

Effects of Ganglionic Blocking Agents on Responses of Ductus Deferens Preparation of Guinea-Pig to Hypogastric Nerve Stimulation

Yamamoto

Nakanishi

1964

Japanese Journal of Pharmacology

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“…Hexamethonium is a bis-quaternary compound, and would have more difficulty in entering a postganglionic sympathetic fibre than mono-quaternary compounds like bretylium or acetylcholine. From the work of Boura, Copp, Duncombe, Green & McCoubrey (1960) it is known that bretylium enters the postganglionic sympathetic fibre in cats, and observations by Stewart, Hutchinson & Szaz (unpublished) have shown that it enters the sympathetic fibres in man in the course of a few minutes.…”

Section: Discussionmentioning

confidence: 99%

The Sympathetic Postganglionic Fibre and the Block by Bretylium; The Block Prevented by Hexamethonium and Imitated by Mecamylamine

Burn

Gibbons

1964

British Journal of Pharmacology and Chemotherapy

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Acetylcholine, in the presence of atropine, has an action like that of sympathetic stimulation. When injected into the splenic artery it causes contraction of the spleen, but this action is blocked by hexamethonium; stimulation of the splenic nerves, however, is still effective. Thus hexamethonium distinguishes between sympathetic nerve stimulation and the action of acetylcholine. If bretylium is used instead of hexamethonium, there is no such distinction, for bretylium blocks the response to nerve stimulation as well as that to acetylcholine. It appeared that hexamethonium might block the action of acetylcholine by preventing its entry into the sympathetic fibre. Acetylcholine has some structural similarity to bretylium, since acetylcholine is a derivative of trimethylammonium and bretylium is a derivative of dimethylethylammonium. It has been found that hexamethonium, pentolinium and hemicholinium , which are all bis-quaternary compounds, block the action of bretylium, presumably by preventing its entry into the fibre. Consistent with the view that ability to enter the fibre is important is the observation that mecamylamine and pempidine, which are ganglion-blocking agents, but not either mono-or bis-quaternary compounds, often abolish the response to stimulation of the sympathetic postganglionic fibre.

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“…One approach is to use bretylium to identify sympathetic nerve terminals. Bretylium enters sympathetic varicosities through uptake-1 sites where it acts as a local anaesthetic and blocks action potential propagation in the secretory terminals and hence transmitter release (Boura & Green, 1960;Brock & Cunnane, 1988b). Bretylium should therefore abolish action potential-evoked Ca 2+ transients in all varicosities containing uptake-1 sites.…”

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Bretylium or 6‐OHDA‐resistant, action potential‐evoked Ca²⁺ transients in varicosities of the mouse vas deferens

Jackson

Cunnane

2002

British J Pharmacology

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Action potential-evoked calcium transients in varicosities in mouse vas deferens were monitored using laser scanning confocal microscopy. Their signi®cance was examined by comparison with excitatory junction potentials (EJPs) and neurogenic contractions, both indirect measurements of transmitter release. Bretylium abolished EJPs, as well as the ATP and NA-mediated phases of contraction. However, bretylium revealed a prominent late component of contraction that was atropine-sensitive. Bretylium abolished calcium transients in 21%, enhanced in 16% and had no e ect in 63% of varicosities examined. Pre-treatment with 6-OHDA reduced NA levels to below detectable levels but many strings of varicosities still responded to nerve impulses with`normal' calcium transients. Varicosities in which calcium transients were abolished by these agents were sympathetic. The identity of those varicosities in which calcium transients were resistant to bretylium (sympathetic but no uptake-1 sites, parasympathetic, sensory) remains to be established.

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The Selective Accumulation of Bretylium in Sympathetic Ganglia and Their Postganglionic Nerves

Cited by 61 publications

References 7 publications

Effects of Ganglionic Blocking Agents on Responses of Ductus Deferens Preparation of Guinea-Pig to Hypogastric Nerve Stimulation

Effects of Ganglionic Blocking Agents on Responses of Ductus Deferens Preparation of Guinea-Pig to Hypogastric Nerve Stimulation

The Sympathetic Postganglionic Fibre and the Block by Bretylium; The Block Prevented by Hexamethonium and Imitated by Mecamylamine

Bretylium or 6‐OHDA‐resistant, action potential‐evoked Ca²⁺ transients in varicosities of the mouse vas deferens

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The Selective Accumulation of Bretylium in Sympathetic Ganglia and Their Postganglionic Nerves

Cited by 61 publications

References 7 publications

Effects of Ganglionic Blocking Agents on Responses of Ductus Deferens Preparation of Guinea-Pig to Hypogastric Nerve Stimulation

Effects of Ganglionic Blocking Agents on Responses of Ductus Deferens Preparation of Guinea-Pig to Hypogastric Nerve Stimulation

The Sympathetic Postganglionic Fibre and the Block by Bretylium; The Block Prevented by Hexamethonium and Imitated by Mecamylamine

Bretylium or 6‐OHDA‐resistant, action potential‐evoked Ca2+ transients in varicosities of the mouse vas deferens

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Bretylium or 6‐OHDA‐resistant, action potential‐evoked Ca²⁺ transients in varicosities of the mouse vas deferens