Abstract
1 The prevention by guanethidine and related agents of the output of noradrenaline induced by low sodium was investigated in rabbit ventricular slices. When external NaCl was reduced, the output of noradrenaline into the medium collected at 30 min intervals, increased and the endogenous levels decreased. These changes induced by replacing sodium with sucrose or choline were not affected either by the omission of calcium and addition of 0.5 mM ethylene glycol-bis(aminoethylether)N,N,N′,N′ tetra-acetic acid (EGTA) or by an increase in the calcium concentration to 10 mM 30 min before sodium deprivation.
2 Guanethidine 4 × 10-6 and 4 × 10-5 M and 4-7-exo-methylene-hexahydroisoindoline-ethyl guanidine (No. 865-123) 4 × 10-5 to 8 × 10-4 M inhibited, in a dose-dependent manner, increases in output of noradrenaline induced by reduction of sodium to 18 mM, while guanethidine 8 × 10-5 M and high doses of bretylium produced no inhibition: the latter two released noradrenaline.
3 The inhibitory actions of guanethidine 4 × 10-5 M and No. 865-123 4 × 10-4 M were prevented by tetracaine 3.3 × 10-4 M, which per se did not modify the output of noradrenaline induced by 18 mM sodium.
4 Accumulation of guanethidine and No. 865-123 in ventricular slices was greater than that noted in striated muscle slices and was dose-, time- and temperature-dependent. Tetracaine 3.3 × 10-4 M did not prevent the accumulation of guanethidine 4 × 10-5 M and No. 865-123 1.1 × 10-6 to 4 × 10-4 M.
5 The guanidine derivatives appear to increase the permeability of adrenergic nerve endings to sodium ions.
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Selected References
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- ANTON A. H., SAYRE D. F. A study of the factors affecting the aluminum oxide-trihydroxyindole procedure for the analysis of catecholamines. J Pharmacol Exp Ther. 1962 Dec;138:360–375. [PubMed] [Google Scholar]
- Abbs E. T., Dodd M. G. The relation between the adrenergic neurone-blocking and noradrenaline-depleting actions of some guanidine derivatives. Br J Pharmacol. 1974 Jun;51(2):237–247. doi: 10.1111/j.1476-5381.1974.tb09653.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BOURA A. L., GREEN A. F. ADRENERGIC NEURONE BLOCKING AGENTS. Annu Rev Pharmacol. 1965;5:183–212. doi: 10.1146/annurev.pa.05.040165.001151. [DOI] [PubMed] [Google Scholar]
- Blaszkowski T. P., Bogdanski D. F. Possible role of sodium and calcium ions in retention and physiological release of norepinephrine by adrenergic nerve endings. Biochem Pharmacol. 1971 Dec;20(12):3281–3294. doi: 10.1016/0006-2952(71)90433-3. [DOI] [PubMed] [Google Scholar]
- Bogdanski D. F., Brodie B. B. The effects of inorganic ions on the storage and uptake of H3-norepinephrine by rat heart slices. J Pharmacol Exp Ther. 1969 Feb;165(2):181–189. [PubMed] [Google Scholar]
- Boullin D. J. The action of extracellular cations on the release of the sympathetic transmitter from peripheral nerves. J Physiol. 1967 Mar;189(1):85–99. doi: 10.1113/jphysiol.1967.sp008156. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burn J. H., Welsh F. The effect of calcium in removing the blocking action of bretylium and guanethidine. Br J Pharmacol Chemother. 1967 Sep;31(1):74–81. doi: 10.1111/j.1476-5381.1967.tb01978.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- CHANG C. C., COSTA E., BRODIE B. B. INTERACTION OF GUANETHIDINE WITH ADRENERGIC NEURONS. J Pharmacol Exp Ther. 1965 Mar;147:303–312. [PubMed] [Google Scholar]
- Garcia A. G., Kirpekar S. M. Release of noradrenaline from the cat spleen by sodium deprivation. Br J Pharmacol. 1973 Apr;47(4):729–747. doi: 10.1111/j.1476-5381.1973.tb08200.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- García A. G., Sánchez-García P. Influence of cocaine and sodium on bretylium uptake by reserpine-treated guinea-pig left atrium. Br J Pharmacol. 1975 Feb;53(2):247–255. doi: 10.1111/j.1476-5381.1975.tb07356.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Giachetti A., Hollenbeck R. A. Extra-vesicular binding of noradrenaline and guanethidine in the adrenergic neurones of the rat heart: a proposed site of action of adrenergic neurone blocking agents. Br J Pharmacol. 1976 Dec;58(4):497–504. doi: 10.1111/j.1476-5381.1976.tb08616.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillis C. N., Paton D. M. Cation dependence of sympathetic transmitter retention by slices of rat ventricle. Br J Pharmacol Chemother. 1967 Mar;29(3):309–318. doi: 10.1111/j.1476-5381.1967.tb01962.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HERTTING G., AXELROD J., PATRICK R. W. Actions of bretylium and guanethidine on the uptake and release of [3H]-noradrenaline. Br J Pharmacol Chemother. 1962 Feb;18:161–166. doi: 10.1111/j.1476-5381.1962.tb01159.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HUKOVIC S., MUSCHOLL E. [Noradrenalin loss from the isolated rabbit heart following sympathetic nerve irritation and its pharmacological alteration]. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1962;244:81–96. [PubMed] [Google Scholar]
- Haeusler G., Haefely W., Huerlimann A. On the mechanism of the adrenergic nerve blocking action of bretylium. Naunyn Schmiedebergs Arch Pharmakol. 1969;265(3):260–277. doi: 10.1007/BF01002340. [DOI] [PubMed] [Google Scholar]
- Hosotani T., Misu Y. Sodium sensitive active transport of bretylium into adrenergic neurons for the development of blockade in rabbit ileum. Arch Int Pharmacodyn Ther. 1977 Apr;226(2):235–245. [PubMed] [Google Scholar]
- Iversen L. L., Kravitz E. A. Sodium dependence of transmitter uptake at adrenergic nerve terminals. Mol Pharmacol. 1966 Jul;2(4):360–362. [PubMed] [Google Scholar]
- Keen P. M., Bogdanski D. F. Sodium and calcium ions in uptake and release of norepinephrine by nerve endings. Am J Physiol. 1970 Sep;219(3):677–682. doi: 10.1152/ajplegacy.1970.219.3.677. [DOI] [PubMed] [Google Scholar]
- Kirpekar S. M., Misu Y. Release of noradrenaline by splenic nerve stimulation and its dependence on calcium. J Physiol. 1967 Jan;188(2):219–234. doi: 10.1113/jphysiol.1967.sp008135. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kirpekar S. M., Wakade A. R., Dixon W., Prat J. C. Effect of cocaine, phenoxybenzamine and calcium on the inhibition of norepinephrine output from the cat spleen by guanthidine. J Pharmacol Exp Ther. 1969 Feb;165(2):166–175. [PubMed] [Google Scholar]
- Kirpekar S. M., Wakade A. R. Factors influencing noradrenaline uptake by the perfused spleen of the cat. J Physiol. 1968 Feb;194(3):609–626. doi: 10.1113/jphysiol.1968.sp008428. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kubo T., Misu Y. Mode of action of guanethidine on adrenergic neurons and its dependence on sodium. Jpn J Pharmacol. 1974 Apr;24(2):307–318. doi: 10.1254/jjp.24.307. [DOI] [PubMed] [Google Scholar]
- Misu Y., Hosotani T., Nakashima E., Nishio H. Effects of calcium and guanethidine on noradrenaline output induced by sodium reduction in rabbit atria. Jpn J Pharmacol. 1977 Oct;27(5):745–748. doi: 10.1254/jjp.27.745. [DOI] [PubMed] [Google Scholar]
- Misu Y., Nishio H. Action of guanethidine on rabbit atrial membranes. Br J Pharmacol. 1978 May;63(1):17–23. doi: 10.1111/j.1476-5381.1978.tb07769.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Misu Y., Nishio H., Hosotani T., Hamano S. A new guanidine derivative: dissociation of the adrenergic neuron blocking activity from local anesthetic activity. Jpn J Pharmacol. 1976 Jun;26(3):367–375. doi: 10.1254/jjp.26.367. [DOI] [PubMed] [Google Scholar]
- SCHANKER L. S., MORRISON A. S. PHYSIOLOGICAL DISPOSITION OF GUANETHIDINE IN THE RAT AND ITS UPTAKE BY HEART SLICES. Int J Neuropharmacol. 1965 Feb;4:27–39. doi: 10.1016/0028-3908(65)90044-4. [DOI] [PubMed] [Google Scholar]
- Starke K., Wagner J., Schümann H. J. Adrenergic neuron blockade by clonidine: comparison with guanethidine and local anesthetics. Arch Int Pharmacodyn Ther. 1972 Feb;195(2):291–308. [PubMed] [Google Scholar]