The Extraneuronal O-methylation of 3H-(+)isoprenaline by Guinea-pig Tracheal Rings in Vitro

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 1981 Dec 1

PMID 7329457

Citations 12

Authors

L G Garland

N V Marrion

G R Martin

Affiliations

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Abstract

Tracheal rings isolated from male guinea-pigs and incubated in Krebs' solution at 37 degrees C O-methylated 3H-(+/-)-isoprenaline by a saturable, high affinity mechanism. 1. With 3H-isoprenaline at 1 mumol . 1-1, O-methyl 3H-(+/-)isoprenaline (3H-OMI) appeared in the tissue with a half-time for approach to steady state of approximately 10 min and was measured in the incubation medium after about 5 min, its concentration increasing linearly thereafter. With 3H-isoprenaline concentrations ranging from 1 to 200 mumol . 1-1, the total formation of 3H-OMI (estimated from that contained in the tissue and the medium) was maintained at steady state rates for up to 60 min, after initial lag times of between 1 and 3 min. O-methylation obeyed Michaelis-Menten saturation kinetics; Km = 6.14 +/- 0.13 mumol . 1-1, Vmax = 0.31 +/- 0.01 nmol . g-1 . min-1. 2. The catechol-O-methyl transferase (COMT) inhibitor U-O521 and the extraneuronal uptake inhibitor corticosterone both reduced O-methylation of 3H-isoprenaline (0.1 mumol . 1-1) by tracheal rings. However, U-O521 was fully inhibitory (IC50 = 2.6 mumol . 1-1), but corticosterone inhibited by only 46% at concentrations up to 1 mmol . 1-1. 3. The O-methylating activity of the "smooth muscle-rich" component of the trachea was approximately three-times greater than for complete tracheal rings. However, considerable activity was also associated with "cartilage-rich", "smooth muscle-poor" sections. This activity did not seem to be associated with endothelial cells. 4. Histamine strongly inhibited O-methylation (IC50 = 30 mumol . 1-1), but two other contractile agonists, 5-hydroxytryptamine and bethanechol, were weakly active and inactive, respectively.

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References

Spilker B, MINATOYA H . The role of bronchoconstrictors in evaluating smooth muscle relaxant activity. Arch Int Pharmacodyn Ther. 1975; 217(2):201-17. View

Graefe K, 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. View

Guldberg H, Marsden C . Catechol-O-methyl transferase: pharmacological aspects and physiological role. Pharmacol Rev. 1975; 27(2):135-206. View

Major H, Sauerwein I, Graefe K . Kinetics of the uptake and metabolism of 3H-(+/-) isoprenaline in the rat submaxillary gland. Naunyn Schmiedebergs Arch Pharmacol. 1978; 305(1):51-63. DOI: 10.1007/BF00497006. View

Graffe K, STEFANO F, Langer S . Preferential metabolism of (-) 3 H-norepinephrine through the deaminated glycol in the rat vas deferens. Biochem Pharmacol. 1973; 22(10):1147-60. DOI: 10.1016/0006-2952(73)90231-1. View

Bryan L, Cole J, ODonnell S . Kinetics of extraneuronal uptake of isoprenaline in trachealis smooth muscle cells: comparison of rat and guinea-pig. J Pharm Pharmacol. 1980; 32(11):793-4. DOI: 10.1111/j.2042-7158.1980.tb13072.x. View

Offermeier J, van den Brink F . The antagonism between cholinomimetic agonists and beta-adrenoceptor stimulants. The differentiation between functional and metaffinoid antagonism. Eur J Pharmacol. 1974; 27(2):206-13. DOI: 10.1016/0014-2999(74)90147-2. View

Foster R . The potentiation of the responses to noradrenaline and isoprenaline of the guinea-pig isolated tracheal chain preparation by desipramine, cocaine, phentolamine, phenoxybenzamine, guanethidine, metanephrine and cooling. Br J Pharmacol Chemother. 1967; 31(3):466-82. PMC: 1557333. DOI: 10.1111/j.1476-5381.1967.tb00412.x. View

Anning E, Bryan L, ODonnell S . The extraneuronal accumulation of isoprenaline in trachea and atria of guinea-pig and cat: a fluorescence histochemical study. Br J Pharmacol. 1979; 65(2):175-82. PMC: 1668618. DOI: 10.1111/j.1476-5381.1979.tb07816.x. View

10.

ODonnell S, Saar N . A histochemical study of extraneuronal accumulation of noradrenaline in the guinea-pig trachea. Br J Pharmacol. 1973; 49(2):267-78. PMC: 1776373. DOI: 10.1111/j.1476-5381.1973.tb08372.x. View

11.

Bryan L, ODonnell S . Comparison of the effects of tropolone, beta-thujaplicin and U-0521 on the extraneuronal accumulation of isoprenaline in guinea-pig trachealis smooth muscle cells. A quantitative fluorescence histochemical study. Naunyn Schmiedebergs Arch Pharmacol. 1979; 307(3):235-41. DOI: 10.1007/BF00505939. View

12.

FURCHGOTT R, Zawadzki J . The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980; 288(5789):373-6. DOI: 10.1038/288373a0. View

13.

Foster R . An uptake of radioactivity from (plus or minus)-3H-isoprenaline and its inhibition by drugs which potentiate the responses to (minus)-isoprenaline in the guinea-pig isolated trachea. Br J Pharmacol. 1969; 35(3):418-27. PMC: 1703357. DOI: 10.1111/j.1476-5381.1969.tb08283.x. View

14.

Bryan L, ODonnell S . Affinities of catecholamines for extraneuronal uptake in smooth muscle cells in trachealis muscle of guinea-pig. Naunyn Schmiedebergs Arch Pharmacol. 1980; 311(2):139-46. DOI: 10.1007/BF00510252. View

15.

Mitchell H, Denborough M . Drug interactions in cat isolated tracheal smooth muscle. Clin Exp Pharmacol Physiol. 1979; 6(3):249-57. DOI: 10.1111/j.1440-1681.1979.tb01246.x. View

16.

Cleland W . The statistical analysis of enzyme kinetic data. Adv Enzymol Relat Areas Mol Biol. 1967; 29:1-32. DOI: 10.1002/9780470122747.ch1. View

17.

Head R, de la Lande I, Irvine R, Johnson S . Uptake and O-methylation of isoprenaline in the rabbit ear artery. Blood Vessels. 1980; 17(5):229-45. DOI: 10.1159/000158253. View

18.

Bonisch H . Further studies on the extraneuronal uptake and metabolism of isoprenaline in the perfused rat heart. Naunyn Schmiedebergs Arch Pharmacol. 1978; 303(2):121-31. DOI: 10.1007/BF00508057. View

19.

Trendelenburg U . A kinetic analysis of the extraneuronal uptake and metabolism of catecholamines. Rev Physiol Biochem Pharmacol. 1980; 87:33-115. DOI: 10.1007/BFb0030896. View

20.

Bryan L, ODonnell S . Kinetic analyses of the mechanisms of action of inhibitors of the extraneuronal uptake of adrenaline in smooth muscle cells of guinea-pig trachea. Naunyn Schmiedebergs Arch Pharmacol. 1981; 315(3):249-54. DOI: 10.1007/BF00499842. View