Adrenotrophic β-receptors in the frog and chicken

Lands, A. M.; Ludueña, F. P.; Buzzo, H.J.

doi:10.1016/0024-3205(69)90230-6

Cited by 17 publications

(4 citation statements)

References 17 publications

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“…The major finding of our study is that the β‐adrenoceptor regulation of I Ca in frog cardiac myocytes is exclusively mediated by β 2 ‐adrenoceptors. This observation is consistent with earlier functional data obtained on whole heart (Lands et al , 1969) or multicellular cardiac preparations of the frog (Stene‐Larsen & Helle, 1978). This finding is also consistent with the fact that the sympathetic nerves carry adrenaline in the frog (Loewi, 1936) and the β 2 ‐receptor is, by definition, an ‘adrenaline receptor’ (Stene‐Larsen & Helle, 1978).…”

Section: Discussionsupporting

confidence: 93%

“…Radioligand binding experiments and competition curve analysis in frog myocardial membrane preparations have shown that the proportion of β 2 ‐receptors may vary from 50% to 100% of the total population of β‐receptors depending on the specific antagonist used to displace the radiolabelled ligand and the individual cell preparation (Hancock et al , 1979; Port et al , 1992). Measurements of force and rate of spontaneous contractions in the isolated heart (Lands et al , 1969) or in isolated auricles (Stene‐Larsen & Helle, 1978) of the frog have shown that the inotropic and chronotropic responses to various sympathomimetic amines are essentially mediated by β 2 ‐adrenoceptors. This suggests that, although present in the sarcolemmal membrane, β 1 ‐adrenoceptors may not be functionally coupled to the effectors involved in the contractile and electrical activities of the frog heart.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacological characterization of the receptors involved in the β‐adrenoceptor‐mediated stimulation of the L‐type Ca²⁺ current in frog ventricular myocytes

Skeberdis

Jurevičius

Fischmeister

1997

British J Pharmacology

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1 The whole-cell patch-clamp was used for studying the e ects of various b 1 -and b 2 -adrenoceptor agonists and antagonists on the L-type Ca current (I Ca ) in frog ventricular myocytes. 2 Dose-response curves for the e ects of isoprenaline (non selective b-agonist), salbutamol (b 2 -agonist), dobutamine (b 1 -agonist) on I Ca were obtained in the absence and presence of various concentrations of ICI 118551 (b 2 -antagonist), metoprolol (b 1 -antagonist) and xamoterol (partial b 1 -agonist) to derive EC 50 (i.e. the concentration of b-agonist at which the response was 50% of the maximum) and E max (the maximal response) values by use of a Michaelis equation. Schild regression analysis was performed to examine whether the antagonists were competitive and to determine the equilibrium dissociation constant (K B ) for the antagonist-receptor complex. 3 Isoprenaline increased I Ca with an EC 50 of 20.0 nM and an E max of 597%. ICI 118551 and metoprolol competitively antagonized the e ect of isoprenaline with a K B of 3.80 nM and 207 nM, respectively. 4 Salbutamol increased I Ca with an EC 50 of 290 nM and an E max of 512%. ICI 118551 and metoprolol competitively antagonized the e ect of salbutamol with a K B of 1.77 nM and 456 nM, respectively. 5 Dobutamine increased I Ca with an EC 50 of 2.40 mM and an E max of 265%. ICI 118551 and metoprolol competitively antagonized the e ect of dobutamine with a K B of 2.84 nM and 609 nM, respectively. 6 Xamoterol had no stimulating e ect on I Ca . However, xamoterol competitively antagonized the stimulating e ects of isoprenaline, salbutamol and dobutamine on I Ca with a K B of 58 ± 64 nM. 7 We conclude that a single population of receptors is involved in the b-adrenoceptor-mediated regulation of I Ca in frog ventricular myocytes. The pharmacological pattern of the response of I Ca to the di erent b-adrenoceptor agonists and antagonists tested suggests that these receptors are of the b 2 -subtype.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Pharmacological characterization of the receptors involved in the β‐adrenoceptor‐mediated stimulation of the L‐type Ca²⁺ current in frog ventricular myocytes

Skeberdis

Jurevičius

Fischmeister

1997

British J Pharmacology

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“…1 Medians of 6 ß, -adrenoceptor-mediated effects for rat (25) and guinea pig (4) epididymal adipose tissue free fatty acid release, mammalian heart rate (26) and force (25,26), rabbit small intestine inhibition (26) and chicken heart excitation (27) with the exception that the estimate for N-cyclopentylbutanefrine is the median (or mean) of only two published values, rat adipose tissue lipolysis and heart force (25). 1 Medians of 6 ß2 -adrenoceptor-mediated effects for guinea pig bronchodilatation (25), dog vasodepression (25), rat uterus inhibition (26), rat diaphragm contraction (26), rat lacticacidemia (8), and frog heart excitation (27) with the exception that the estimate for N-cyclopentylbutanefrine is the median of only three published values, guinea pig broncho dilatation (25), dog vasodepression (25), and rat lacticacidemia (8).…”

Section: Methodsmentioning

confidence: 99%

Relative Lipolytic Activities of Selected Catecholamines in the Mouse

Arnold¹,

McAuliff²

1976

Pharmacology

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The adipokinetic activities, relative to isoproterenol as 1,000, in sedated, phenoxybenzamine pretreated unfasted mice were: norepinephrine 540, epinephrine 330, N-t-butylnorepinephrine 130, isoetharine 30 and N-cyclopentylbutanefrine 10. These relative activities correlate (r = 0.88) with the medians of some previously defined β₁-adrenoceptor activities, but not (r = < 0.1) with the medians of some previously defined β₂-adrenoceptor activities. These findings are in accord with the previously suggested view that an α-, β₁-, β₂-adrenoceptor concept is in better accord with experimental evidence than is an α- and β-adrenoceptor one.

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“…The quantitative analysis of cocaine-induced sensitization of guinea-pig trachea and atria to noradrenaline shows that concentrations used in pharmacologi- burg, 1972;Guimaraes & Paiva, 1977), the volume/ surface ratio of isolated tissue preparations (Ebner & Waud, 1978) (Lands, Arnold, McAuliff, Luduena & Brown, 1967a;Lands, Luduena & Buzzo, 1967b) noradrenaline has been classified as a #I selective agonist and the guinea-pig trachea a predominantly 2 selective organ. The subsequent finding that salbutamol is more potent than noradrenaline in guinea-pig trachea has led to the assumption that salbutamol is a /2 selective agonist.…”

Section: Discussionmentioning

confidence: 99%

Errors in the Measurement of Agonist Potency‐ratios Produced by Uptake Processes: A General Model Applied to Β‐adrenoceptor Agonists

Kenakin

1980

British J Pharmacology

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I The sensitization of guinea-pig atria and trachea to noradrenaline, isoprenaline, and salbutamol, produced by an inhibitor of neuronal (cocaine) and extraneuronal (metanephrine) uptake, was studied quantitatively. The data were compared to a theoretical model. 2 Cocaine produced near maximal sensitization to noradrenaline in guinea-pig atria (5 fold) at concentrations which produced only partial sensitization in guinea-pig trachea (4.7 fold sensitization of a maximum 11 fold). These results agreed with the model which predicts that there is a direct relationship between the amount of uptake inhibitor required to produce full sensitization and the magnitude of maximal sensitization demonstrable in the tissue. This makes extrapolation of uptake inhibition concentrations from tissue to tissue a potentially erroneous practice. 3 In normal trachea, salbutamol is 20 times more potent than noradrenaline but this difference is abolished (to 0.9 times) by cocaine (100 gm). This reduction of potency-ratio is due to the selective cocaine-induced sensitization of trachea to noradrenaline and raises a serious objection to the classification of salbutamol as a P2 selective agonist.4 Metanephrine produced very little sensitization of trachea to isoprenaline. Experiments with salbutamol showed metanephrine to be a simple competitive antagonist of ,B-adrenoceptors (pKb = 4.3) and that this receptor antagonism masked sensitization to isoprenaline. 5 A theoretical model indicates that an inhibitor of agonist uptake requires a remarkable degree of selectivity for the uptake mechanism (i.e. Kb for receptors 104 x Kg for uptake sites) to demonstrate tissue sensitization to the agonist. This analysis and the data with metanephrine indicate that a sinistral shift of the concentration-response curve is a poor indicator of the importance of uptake mechanisms in an isolated tissue. 6 An alternate method to determine the importance of agonist-uptake effects on concentrationresponse curves is described which utilizes agonist potency ratios. Agonist potency ratios in guineapig atria and trachea showed that the bronchoselectivity demonstrated by salbutamol (with respect to isoprenaline) is reduced from 54 to 7.8 by metanephrine reflecting the importance of extraneuronal uptake in trachea.

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Adrenotrophic β-receptors in the frog and chicken

Cited by 17 publications

References 17 publications

Pharmacological characterization of the receptors involved in the β‐adrenoceptor‐mediated stimulation of the L‐type Ca²⁺ current in frog ventricular myocytes

Pharmacological characterization of the receptors involved in the β‐adrenoceptor‐mediated stimulation of the L‐type Ca²⁺ current in frog ventricular myocytes

Relative Lipolytic Activities of Selected Catecholamines in the Mouse

Errors in the Measurement of Agonist Potency‐ratios Produced by Uptake Processes: A General Model Applied to Β‐adrenoceptor Agonists

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Adrenotrophic β-receptors in the frog and chicken

Cited by 17 publications

References 17 publications

Pharmacological characterization of the receptors involved in the β‐adrenoceptor‐mediated stimulation of the L‐type Ca2+ current in frog ventricular myocytes

Pharmacological characterization of the receptors involved in the β‐adrenoceptor‐mediated stimulation of the L‐type Ca2+ current in frog ventricular myocytes

Relative Lipolytic Activities of Selected Catecholamines in the Mouse

Errors in the Measurement of Agonist Potency‐ratios Produced by Uptake Processes: A General Model Applied to Β‐adrenoceptor Agonists

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Pharmacological characterization of the receptors involved in the β‐adrenoceptor‐mediated stimulation of the L‐type Ca²⁺ current in frog ventricular myocytes

Pharmacological characterization of the receptors involved in the β‐adrenoceptor‐mediated stimulation of the L‐type Ca²⁺ current in frog ventricular myocytes