Abstract
Kitten coronary arteries and atria incubated with [3H]-(-)-noradrenaline or [3H]-(+/-)-isoprenaline showed concentration- and temperature-dependent accumulation of amines (unchanged and/or as metabolites). In addition, coronary arteries incubated with [3H]-(+/-)-isoprenaline showed temperature-insensitive amine accumulation due to binding to connective tissue fibres. 2 With low concentrations of [3H]-(-)-noradrenaline (20 ng/ml) accumulation of radioactivity in both tissues was neuronal since it was reduced by desipramine, metaraminol or cocaine but not by the extraneuronal inhibitor, cortisol. 3 In coronary arteries incubated with [3H]-(+/-)-isoprenaline (5 microgram/ml) for 1 or 10 min, uptake was extraneuronal since it was inhibited by cortisol, 17beta-oestradiol or phenoxybenzamine. 4 Atria incubated with (+/-)-isoprenaline (5 to 1000 microgram/ml) showed non-neuronal, biphasic accumulation of amine. There was a high capacity, low affinity initial uptake process (apparent Km 136 micron) which was resistant to steroidal extraneuronal uptake inhibitors but which could be abolished by phenoxybenzamine. A slower uptake occurred after 2 min which was sensitive to steroidal and other extraneuronal uptake inhibitors. 5 Inhibition of uptake processes did not alter sensitivity of coronary arteries to dilator effects of catecholamines. However, experiments with extraneuronal uptake inhibitors were limited by the relaxant effects of cortisol and 17beta-oestradiol themselves. 6 In atria inhibition of neuronal uptake by desipramine or cocaine led to supersensitivity to (-)-noradrenaline but not to (-)-adrenaline or (+/-)-isoprenaline. Chronotropic responses to (-)-noradrenaline were increased five fold and inotropic responses three fold.
Full text
PDF











Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bönisch H., Trendelenburg U. Extraneuronal removal, accumulation and O-methylation of isoprenaline in the perfused heart. Naunyn Schmiedebergs Arch Pharmacol. 1974;283(2):191–218. doi: 10.1007/BF00501145. [DOI] [PubMed] [Google Scholar]
- Bönisch H., Uhlig W., Trendelenburg U. Analysis of the compartments involved in the extraneuronal storage and metabolism of isoprenaline in the perfused heart. Naunyn Schmiedebergs Arch Pharmacol. 1974;283(3):223–244. doi: 10.1007/BF00499185. [DOI] [PubMed] [Google Scholar]
- Cornish E. J., Miller R. C. Comparison of the beta-adrenoceptors in the myocardium and coronary vasculature of the kitten heart. J Pharm Pharmacol. 1975 Jan;27(1):23–30. doi: 10.1111/j.2042-7158.1975.tb09373.x. [DOI] [PubMed] [Google Scholar]
- Cornish E. J., Miller R. C., Tolmer P. R. An isolated perfused coronary artery preparation from the kitten. J Pharm Pharmacol. 1974 Sep;26(9):733–735. doi: 10.1111/j.2042-7158.1974.tb09360.x. [DOI] [PubMed] [Google Scholar]
- De la Lande I. S., Frewin D., Waterson J. G. The influence of sympathetic innervation on vascular sensitivity to noradrenaline. Br J Pharmacol Chemother. 1967 Sep;31(1):82–93. doi: 10.1111/j.1476-5381.1967.tb01979.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Denn M. J., Stone H. L. Automic innervation of dog coronary arteries. J Appl Physiol. 1976 Jul;41(1):30–35. doi: 10.1152/jappl.1976.41.1.30. [DOI] [PubMed] [Google Scholar]
- Gillespie J. S., Muir T. C. Species and tissue variation in extraneuronal and neuronal accumulation of noradrenaline. J Physiol. 1970 Mar;206(3):591–604. doi: 10.1113/jphysiol.1970.sp009032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldie R. G. The effects of hydrocortisone on responses to and extraneuronal uptake of (-)-isoprenaline in cat and guinea-pig atria. Clin Exp Pharmacol Physiol. 1976 May-Jun;3(3):225–233. doi: 10.1111/j.1440-1681.1976.tb02668.x. [DOI] [PubMed] [Google Scholar]
- Graefe K. H., Trendelenburg U. The effect of hydrocortisone on the sensitivity of the isolated nictitating membrane to catecholamines: Relationship to extraneuronal uptake and metabolism. Naunyn Schmiedebergs Arch Pharmacol. 1974;286(1):1–48. doi: 10.1007/BF00499103. [DOI] [PubMed] [Google Scholar]
- Guldberg H. C., Marsden C. A. Catechol-O-methyl transferase: pharmacological aspects and physiological role. Pharmacol Rev. 1975 Jun;27(2):135–206. [PubMed] [Google Scholar]
- Henseling M., Eckert E., Trendelenburg U. The distribution of 3H-(+/-)noradrenaline in rabbit aortic strips after inhibition of the noradrenaline-metabolizing enzymes. Naunyn Schmiedebergs Arch Pharmacol. 1976;292(3):205–217. doi: 10.1007/BF00517381. [DOI] [PubMed] [Google Scholar]
- IVERSEN L. L. THE UPTAKE OF NORADRENALINE BY THE ISOLATED PERFUSED RAT HEART. Br J Pharmacol Chemother. 1963 Dec;21:523–537. doi: 10.1111/j.1476-5381.1963.tb02020.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Iversen L. L., Salt P. J. Inhibition of catecholamine Uptake-2 by steroids in the isolated rat heart. Br J Pharmacol. 1970 Nov;40(3):528–530. doi: 10.1111/j.1476-5381.1970.tb10637.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jacobowitz D. A study of the extraneural uptake of norepinephrine in the perfused heart of the guinea-pig. Eur J Pharmacol. 1971;15(3):274–284. doi: 10.1016/0014-2999(71)90093-8. [DOI] [PubMed] [Google Scholar]
- Kalsner S., Frew R. D., Smith G. M. Mechanism of methylxanthine sensitization of norepinephrine responses in a coronaryartery. Am J Physiol. 1975 Jun;228(6):1702–1707. doi: 10.1152/ajplegacy.1975.228.6.1702. [DOI] [PubMed] [Google Scholar]
- Kalsner S. Sensitization of noradrenaline responses by inhibitors of extraneuronal uptake in a coronary artery preparation. Br J Pharmacol. 1974 Jul;51(3):453–455. doi: 10.1111/j.1476-5381.1974.tb10682.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaumann A. J. Potentiation of the effects of isoprenaline and noradrenaline by hydrocortisone in cat heart muscle. Naunyn Schmiedebergs Arch Pharmacol. 1972;273(1):134–153. doi: 10.1007/BF00508086. [DOI] [PubMed] [Google Scholar]
- Kaumann A. J., Wittmann R., Birnbaumer L., Hoppe B. H. Activation of myocardial beta-adrenoceptors by the nitrogen-free low affinity ligand 3',4'-dihydroxy-alpha-methylpropiophenone (U-0521). Naunyn Schmiedebergs Arch Pharmacol. 1977 Feb;296(3):217–228. doi: 10.1007/BF00498688. [DOI] [PubMed] [Google Scholar]
- MCEWEN L. M. The effect on the isolated rabbit heart of vagal stimulation and its modification by cocaine, hexamethonium and ouabain. J Physiol. 1956 Mar 28;131(3):678–689. doi: 10.1113/jphysiol.1956.sp005493. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Madsen N. P. Use of toluene/triton X-100 scintillation mixture for counting C14-protein radioactivity. Anal Biochem. 1969 Jun;29(3):542–544. doi: 10.1016/0003-2697(69)90341-8. [DOI] [PubMed] [Google Scholar]
- Malor R., Griffin C. J., Taylor S. Innervation of the blood vessels in guinea-pig atria. Cardiovasc Res. 1973 Jan;7(1):95–104. doi: 10.1093/cvr/7.1.95. [DOI] [PubMed] [Google Scholar]
- Mireylees S. E., Foster R. W. Letter: 3-methoxyisoprenaline: a potent selective Uptake2 inhibitor. J Pharm Pharmacol. 1973 Oct;25(10):833–835. doi: 10.1111/j.2042-7158.1973.tb09954.x. [DOI] [PubMed] [Google Scholar]
- Nishioka M. Pharmacological responses of the smooth muscle of the pig's excised coronary artery, especially in relation to Ca. Kobe J Med Sci. 1971 Sep;17(3):129–159. [PubMed] [Google Scholar]
- Powis G. Binding of catecholamines to connective tissue and the effect upon the responses of blood vessels to noradrenaline and to nerve stimulation. J Physiol. 1973 Oct;234(1):145–162. doi: 10.1113/jphysiol.1973.sp010339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Uhlig W., Fiebig R., Trendelenburg U. The effect of corticosterone on the fluxes of 3H-normetanephrine into and out of the extraneuronal compartments of the perfused rat heart. Naunyn Schmiedebergs Arch Pharmacol. 1976 Oct;295(1):45–50. doi: 10.1007/BF00509771. [DOI] [PubMed] [Google Scholar]
- de la Lande I., Harvey J. A., Holt S. Response to the rabbit coronary arteries to autonomic agents. Blood Vessels. 1974;11(5-6):319–337. doi: 10.1159/000158025. [DOI] [PubMed] [Google Scholar]