Reversal of Guanethidine Blockade of Sympathetic Nerve Terminals by Tetraethylammonium and 4‐aminopyridine

Kirpekar, M; Kirpekar, S. M.; Prat, J. C.

doi:10.1111/j.1476-5381.1978.tb07008.x

Cited by 14 publications

(7 citation statements)

References 8 publications

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“…A third possibility is that guanidine allows greater than normal amounts of calcium to accumulate inside the sympathetic nerve terminals during an action potential to reverse guanethidine blockade of NA release. TEA and 4-AP have also been shown to reverse guanethidine blockade (Kirpekar et al, 1978). Since all three agents are known to enhance the calcium concentration in the nerve terminals (Lundh et al, 1977), and since little is known regarding their ability to open the sodium channels which have been blocked by a local anaesthetic, we would like to suggest that antagonism between guanidine and guanethidine probably involves mobilization by guanidine of calcium within the sympathetic nerve terminals.…”

Section: Effect Of Graded Concentrations Of Guanidine On Noradrenalinmentioning

confidence: 99%

“…An alternative suggestion is that guanethidine or bretylium may depress NA release by blocking the increase in calcium permeability associated with evoked release (Kirpekar, Wakade, Dixon & Prat, 1969;Krauss, Carpenter & Kopin, 1970;Kirpekar et al, 1978). Since the effect of guanidine appears to be related in some way to intraneuronal calcium concentration, it was of interest to determine whether guanidine, like TEA and 4-AP (Kirpekar et al, 1978), would reverse the guanethidine blockade of sympathetic nerves. Figure 6 shows that guanidine reversed the inhibition of NA release by guanethidine during nerve stimulation at 10 Hz.…”

Section: Effect Of Graded Concentrations Of Guanidine On Noradrenalinmentioning

confidence: 99%

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Effect of Guanidine on Release of Noradrenaline From the Perfused Spleen of the Cat

Hirsch¹,

Kirpekar²,

Prat³

1979

British J Pharmacology

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1 Guanidine increased noradrenaline (NA) output at 5 Hz by 3 to 6 fold, and doubled it at 30 Hz. Onset of maximum activity was slow, and reversal was also slow. Output of NA induced by potassium, sodium deprivation, or tyramine was not affected. 2 NA output was doubled at low concentrations (1 to 2 mM) of guanidine, but maximal effect was obtained at 4 mM. At 10 mM, spontaneous release was occasionally observed. 3 The effect of guanidine on NA release was related to the external calcium concentration. Outputs which previously have been shown to be insignificant at 5 Hz in 0.25 and 0.75 mm calcium-Krebs solution were markedly enhanced by guanidine. Guanidine enhanced release at all calcium concentrations up to 7.5 mm, but maximum output was obtained at 2.5 mm. 4 Guanidine had no effect on the recovery of intra-arterially infused NA. 5 The effects of guanidine and tetraethyl-ammonium (TEA) on NA release at 5 Hz were additive. 6 Guanidine reversed the inhibition of NA release by guanethidine during nerve stimulation at 5 and 10 Hz, and the NA output increased nearly 2.5 fold after repeated stimulation of the nerves. Guanidine was less effective in reversing the inhibitory effects of guanethidine on NA release at 30 Hz. 7 Guanidine did not affect release of catecholamines (CA) from the perfused cat adrenal gland by splanchnic nerve stimulation. 8 It is suggested that guanidine enhances NA release partly by increasing the influx of calcium into the neurone during an action potential, and also by interfering with intracellular binding ot calcium.

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Section: Effect Of Graded Concentrations Of Guanidine On Noradrenalinmentioning

confidence: 99%

Section: Effect Of Graded Concentrations Of Guanidine On Noradrenalinmentioning

confidence: 99%

Effect of Guanidine on Release of Noradrenaline From the Perfused Spleen of the Cat

Hirsch¹,

Kirpekar²,

Prat³

1979

British J Pharmacology

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“…These observations suggest that antagonism of the tracheal relaxant actions of KCOs is a property shared by several agents classically described (Louis & Howes, 1990) as adrenergic neurone blocking agents. The ability of the adrenergic neurone blocking agents selectively to inhibit the airways smooth muscle relaxant actions of the KCOs without antagonizing agonists at P-adrenoceptors or alkylxanthines is shared both by sulphonylureas such as glibenclamide (Murray et al, 1989;Black et al, 1990;Nielsen-Kudsk et al, 1990;Berry et al, 1991;Raeburn & Brown, 1991) and by phentoamine (Murray et al, 1989;McPherson & Angus, 1990 Kirpekar et al (1978) observed that the K+-channel inhibitors tetraethylammonium (TEA) and 4-aminopyridine (4-AP) could reverse the ability of guanethidine to inhibit the neural release of noradrenaline in the in situ perfused spleen of the cat. Stutzin et al (1983) observed that the K+-channel inhibitor, apamin, could antagonize guanethidine in inhibiting contractile responses to the electrical stimulation of nerves in the guinea-pig isolated vas deferens.…”

Section: Discussionmentioning

confidence: 99%

Tracheal relaxation induced by potassium channel opening drugs: its antagonism by adrenergic neurone blocking agents

Berry

Small

Foster

1992

British J Pharmacology

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1 We have studied the ability of some adrenergic neurone blocking agents to inhibit the tracheal relaxant actions of isoprenaline, theophylline and the potassium channel openers (KCOs) BRL 38227, pinacidil and RP 52891. 2 BRL 38227, isoprenaline, pinacidil, RP 52891 and theophylline each caused concentration-dependent suppression of the spontaneous tone of guinea-pig isolated trachealis. The maximal relaxant effects of isoprenaline and pinacidil were equal to that of theophylline. In contrast, the maximal effects of BRL 38227 and RP 52891 were approximately 85-95% of that of theophylline.3 Guanethidine (5-5001iM) did not itself modify the spontaneous tone of the trachealis muscle but antagonized BRL 38227 in a concentration-dependent manner. Guanethidine (50 LM) also antagonized pinacidil and RP 52891. However, guanethidine did not antagonize either isoprenaline or theophylline. 4 Bretylium (50 LM) did not itself modify the spontaneous tone of the trachealis muscle but antagonized BRL 38227, pinacidil and RP 52891. Bretylium did not antagonize either isoprenaline or theophylline. 5Guanidine (50 and 500 j1M) did not itself modify the spontaneous tone of the trachea and failed to modify the tracheal relaxant activity both of BRL 38227 and theophylline.6 BRL 38227 (1 and 10 fiM) stimulated, in a concentration-dependent manner, the efflux of 86Rb+ from strips of bovine trachealis muscle that had been pre-loaded with the radiotracer. Guanethidine (50 iM), bretylium (50 JiM) and debrisoquine (50 jiM) did not themselves modify the efflux of 86Rb+ from bovine trachealis but each of these agents markedly inhibited the stimulant effect of BRL 38227 (10 jiM) on 86Rb+ efflux. 7 It is concluded that the adrenergic neurone blocking agents guanethidine and bretylium can inhibit the tracheal relaxant actions of KCOs such as BRL 38227, pinacidil and RP 52891 without antagonizing isoprenaline or theophylline. The ability of the adrenergic neurone blocking agents to antagonize BRL 38227 in promoting 86Rb+ efflux from trachealis muscle may suggest that the adrenergic neurone blocking agents act to prevent the opening of the plasmalemmal K+-channel that is involved in the tracheal relaxant actions of the KCOs.

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“…The experiments with apamin and tetraethylammonium also sug gest that an increase in potassium conduc tance inducing hyperpolarization of the vas cular smooth muscle cells is probably not the mechanism underlying the relaxation. Te traethylammonium enhances transmitter re lease [47,48] even in calcium-dependent nerves which release transmitter indepen dently from sodium channels [32,33] in the canine coronary artery, tetraethylammoni um did not enhance the relaxation to elec trical stimulation.…”

Section: Discussionmentioning

confidence: 99%

Tetrodotoxin-Insensitive Relaxation of Coronary Arterial Smooth Muscle to Electrical Stimulation: Possible Involvement of a Dopaminergic Mechanism

Félétou¹,

Vanhoutte²

1989

J Vasc Res

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Experiments were designed to determine the mechanism by which electrical stimulation causes tetrodotoxin-insensitive relaxation in isolated arteries. Rings of left anterior descending coronary arteries of dogs, pigs and calves were suspended in organ chambers between platinum electrodes. Experiments were performed after treatment with phenoxybenzamine and in the presence of propranolol. Calcium-free solution and calcium antagonists reduced the relaxation. Chemical denervation with 6-hydroxydopamine reduced the relaxation induced by electrical stimulation; in the presence of pargyline, the inhibitor of monoamine oxidase, it was virtually abolished. The nonselective dopaminergic antagonist droperidol and the selective DA₁-dopaminergic antagonist SKF R83566 caused a concentration-dependent inhibition of the relaxation; the DA₂-dopaminergic antagonist domperidone was ineffective. High concentrations of dopamine induced relaxation of the coronary smooth muscle; the relaxation was inhibited by SKF R83566 but not by droperidol. These results suggest that electrical stimulation causes relaxation by liberating an endogenous vasodilator substance, which acts on DA₁-dopaminergic receptors of the coronary smooth muscle.

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Reversal of Guanethidine Blockade of Sympathetic Nerve Terminals by Tetraethylammonium and 4‐aminopyridine

Cited by 14 publications

References 8 publications

Effect of Guanidine on Release of Noradrenaline From the Perfused Spleen of the Cat

Effect of Guanidine on Release of Noradrenaline From the Perfused Spleen of the Cat

Tracheal relaxation induced by potassium channel opening drugs: its antagonism by adrenergic neurone blocking agents

Tetrodotoxin-Insensitive Relaxation of Coronary Arterial Smooth Muscle to Electrical Stimulation: Possible Involvement of a Dopaminergic Mechanism

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