Some evidence for the extraneuronal uptake of rimiterol and its metabolism by catechol-<i>O</i>-methyltransferase in guinea-pig trachealis smooth muscle cells

We assessed in protein droplet models the potential use of the formaldehyde condensation method for histochemical demonstration of a wide range of catecholamines and resorcinolamines. The experiments showed that all of the amines tested, except salbutamol and carbuterol, formed fluorophores, and that the fluorescence was specific [i.e., there was no fluorescence in the absence of formaldehyde, the fluorescence was quenched by water, and the fluorophores were subject to photodecomposition by the exciting (405-nm) light]. Peak wavelengths of the emission spectra were 480-485 nm for fluorophores of resorcinolamine derivatives. The fluorescence intensity of the catecholamines was greater than that of the resorcinolamines. Fluorophore formation was not hindered by substitution of t-butyl, phenylisoprophyl, or p-hydroxyphenylisopropyl on the amino-N in catecholamines (t-butylnorepinephrine, Cc24, Cc25, respectively) or resorcinolamines (terbutaline, Th1161, fenoterol, respectively), and fluorophores also formed for catecholamines with the amino-N in a ring structure (rimiterol) or with a long alkyl chain substituted on the amino-N (hexoprenaline). Our study showed that fluorescence microphotometry can be used to detect a range of drugs that are catecholamines or resorcinolamines, and hence it should be possible to use this technique to study the properties of dissipation of these amines in tissues.

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Catechol-O-methyltransferase: substrate-specificity and stereoselectivity for β-adrenoceptor agents

Raxworthy

Youde

Gulliver

1986

Xenobiotica

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Isoprenaline, isoetharine, rimiterol, dobutamine and nadolol were investigated as substrates for purified pig-liver catechol-O-methyltransferase using a sensitive spectrophotometric assay. Kinetic parameters, Km and Vmax, were defined and the apparent first-order rate constant (Vmax/Km) was derived. On the basis of the apparent first-order rate constant, rimiterol was found to be a 1.5-fold and dobutamine a 5-fold better substrate for catechol-O-methyltransferase than isoprenaline; isoetharine shows no improvement over isoprenaline. Nadolol is not a substrate for catechol-O-methyltransferase. O-Methylation of isoprenaline- and noradrenaline-enantiomers was found to be stereoselective: catechol-O-methyltransferase shows selectivity towards the laevo (-) isomer with respect to the (+) form or racemic mixture. The investigation indicated stereochemical and steric determinants important in the interaction of catechol-O-methyltransferase with physiologically and clinically important beta-adrenoceptor agents.

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Some evidence for the extraneuronal uptake of rimiterol and its metabolism by catechol-O-methyltransferase in guinea-pig trachealis smooth muscle cells

Cited by 3 publications

References 15 publications

The Extraneuronal Uptake and Metabolism of Catecholamines

The Extraneuronal Uptake and Metabolism of Catecholamines

Demonstration of catecholamine and resorcinolamine derivatives as formaldehyde-induced fluorescence in protein models.

Catechol-O-methyltransferase: substrate-specificity and stereoselectivity for β-adrenoceptor agents

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