Indications for the existence of two types of cardiac β-adrenergic receptors

Dreyer, Anton C.; Offermeier, J

doi:10.1016/s0031-6989(75)80019-1

Cited by 22 publications

(7 citation statements)

References 8 publications

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“…In these experiments, proprano-lo1 produced concentration-related rightward shifts of noradrenaline concentration-response curves and when these shifts were used to construct Arunlakshana & Schild (1959) plots straight lines were obtained with slopes that did not differ from unity. The pA2 values obtained from the Arunlakshana & Schild plots were between 8.1 and 8.4 and are similar to values reported for the antagonism by propranolol of guinea-pig isolated atria responses to isoprenaline (8.0-8.6;Dryer & Offermeier, 1975;Seigl, Rossi & Orzechowski, 1979). These results indicate that noradrenaline is acting solely at /3-adrenoceptors in all three tissues.…”

Section: Discussionsupporting

confidence: 83%

α‐adrenoceptors do not contribute to the chronotropic or inotropic responses of the avian heart to noradrenaline

Chess-Williams

Austin

O'Brien

1991

Journal of Autonomic Pharmacology

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1. The chronotropic and inotropic responses of the young chick heart to noradrenaline have been investigated in isolated right atria, left atria and ventricular strips from 14-day-old chicks. 2. In the presence of desipramine and metanephrine to inhibit amine uptake, concentration-response curves to noradrenaline in all three tissues were shifted to the right by propranolol (1 microM) but were not altered by the presence of either phentolamine (5 microM) or prazosin (10 microM). 3. Similar results were obtained in the presence of cocaine (10 microM) and corticosterone (10 microM) to inhibit amine uptake. Propranolol (0.3-3.0 microM) produced rightward shifts of noradrenaline concentration-response curves which gave pA2 values of 8.1-8.4. Phentolamine (5 microM), in contrast, did not affect responses to noradrenaline in any tissue, either in the absence or presence of propranolol (1 microM). 4. Isoprenaline produced positive chronotropic responses in right atria and positive inotropic responses in left atria and ventricular strips. Methoxamine elicited positive inotropic responses in left atria but only negative chronotropic responses in right atria and negative inotropic responses in ventricular strips. 5. These results demonstrate that cardiac responses to noradrenaline in the chick heart are mediated via beta-adrenoceptors only, and that cardiac alpha-adrenoceptors are not involved in these responses.

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Section: Discussionsupporting

confidence: 83%

α‐adrenoceptors do not contribute to the chronotropic or inotropic responses of the avian heart to noradrenaline

Chess-Williams

Austin

O'Brien

1991

Journal of Autonomic Pharmacology

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“…Similar values were also obtained for the positive inotropic and chronotropic responses of left and right atria to isoprenaline, as shown previously 1981). Yet these agonists exhibited a rate-selectivity at 38°C, the EC50 values being less for the rate responses, and the possibility has been suggested that the Padrenoceptors mediating the positive inotropic and chronotropic responses can be distinguished (Dreyer & Offermeier, 1975;Giudicelli, 1975). However, the bulk of pharmacological evidence refutes this proposal Kaumann, Mclnerny, Gilmour & Blinks, 1980), for the guinea-pig at least, where only PI-adrenoceptors mediate these responses (Zaagsma, Oudhof, Van der Heijden & Plantje, 1979).…”

Section: Discussionsupporting

confidence: 83%

Temperature‐induced changes in dissociation constants (K_A) of agonists at cardiac β‐adrenoceptors determined by use of the irreversible antagonist Ro 03–7894

Broadley

Williams

1983

British J Pharmacology

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1The positive inotropic responses of guinea-pig left atria and papillary muscles and positive chronotropic responses of right atria to sympathomimetic amines were examined at 380 and 30°C. 2 At the lower temperature, supersensitivity to orciprenaline and isoprenaline was exhibited as shifts of the dose-response curves to the left and significant reductions in EC50 values. 3 This supersensitivity could not be attributed to reduced metabolism since the experiments were performed in the presence of metanephrine (10-5M) and U-0521 (3',4'-dihydroxy-2-methylpropiophenone) (10-4M) as inhibitors of extraneuronal uptake and catechol-Omethyltransferase (COMT) respectively, and the agonists are not susceptible to neuronal uptake. 4 After incubation of the tissues with Ro 03-7894 (1-(5-chloracetylaminobenzfuran-2-yl)-2-isopropylaminoethanol), followed by its prolonged washout (> 2h), the maximum responses to isoprenaline and orciprenaline were depressed, confirming the apparently irreversible Iadrenoceptor antagonism. 5 Dissociation constants (KA) for isoprenaline and orciprenaline were determined from the equiactive concentrations obtained before (A) and after (A') incubation with Ro 03-7894, plotted as 1/A against 1/A' (KA = (slope -1)/intercept). 6 KA values were the same for orciprenaline in the three cardiac preparations and for isoprenaline in the atria. This applied at 380 and 30°C and indicates that the P-adrenoceptors mediating the inotropic and chronotropic responses of the guinea-pig heart do not differ. 7 The KA values of both agonists were, however, consistently and significantly lower at 300 than at 38°C, indicating an increase in affinity. 8 It is concluded that hypothermia-induced supersensitivity of cardiac tissue to sympathomimetic amines is associated with an increase in their affinity for the ,B-adrenoceptors.

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“…The question whether the ,B-adrenoceptors mediating the positive inotropic and chronotropic responses of the heart are identical has been examined by the use of both antagonists and agonists. Evidence from antagonist studies is conflicting since there are reports of preferential antagonism of both the chronotropic (Dreyer & Offermeier, 1975) and inotropic responses (Fenyvesi, 1972). A small selectivity for the inotropic response was also observed by Blinks (1967), but he did not consider this was sufficient for subclassification of the ,B-adrenoceptors.…”

Section: Introductionmentioning

confidence: 99%

Functional Antagonism as a Means of Determining Dissociation Constants and Relative Efficacies of Sympathomimetic Amines in Guinea‐pig Isolated Atria

Broadley

Nicholson

1979

British J Pharmacology

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I The positive inotropic and chronotropic responses to sympathomimetic amines were examined in guinea-pig isolated atria.2 The order of potency measured from EC3o values was isoprenaline > orciprenaline > salbutamol > fenoterol > terbutaline. Terbutaline and salbutamol were partial agonists on rate and together with orciprenaline and fenoterol also on tension responses. 3 Functional antagonism by carbachol caused a rightwards shift of the dose-response curve and depression of the maximum response. The rate maxima for orciprenaline, fenoterol and terbutaline were above that of isoprenaline. All the tension maxima were below isoprenaline. 4 Dissociation constants (KA) and relative efficacies (er) were determined by analogy with irreversible antagonism. 5 The relative orders of affinity (KA) were isoprenaline > orciprenaline > fenoterol > salbutamol > terbutaline. Affinities were identical on rate and tension. 6 The relative efficacies were all greater than isoprenaline for rate responses. On tension they were the same or less than isoprenaline. 7 The implications of these results are discussed, in particular the fact that a partial agonist has a greater efficacy than a full agonist.

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Indications for the existence of two types of cardiac β-adrenergic receptors

Cited by 22 publications

References 8 publications

α‐adrenoceptors do not contribute to the chronotropic or inotropic responses of the avian heart to noradrenaline

α‐adrenoceptors do not contribute to the chronotropic or inotropic responses of the avian heart to noradrenaline

Temperature‐induced changes in dissociation constants (K_A) of agonists at cardiac β‐adrenoceptors determined by use of the irreversible antagonist Ro 03–7894

Functional Antagonism as a Means of Determining Dissociation Constants and Relative Efficacies of Sympathomimetic Amines in Guinea‐pig Isolated Atria

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Indications for the existence of two types of cardiac β-adrenergic receptors

Cited by 22 publications

References 8 publications

α‐adrenoceptors do not contribute to the chronotropic or inotropic responses of the avian heart to noradrenaline

α‐adrenoceptors do not contribute to the chronotropic or inotropic responses of the avian heart to noradrenaline

Temperature‐induced changes in dissociation constants (KA) of agonists at cardiac β‐adrenoceptors determined by use of the irreversible antagonist Ro 03–7894

Functional Antagonism as a Means of Determining Dissociation Constants and Relative Efficacies of Sympathomimetic Amines in Guinea‐pig Isolated Atria

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Temperature‐induced changes in dissociation constants (K_A) of agonists at cardiac β‐adrenoceptors determined by use of the irreversible antagonist Ro 03–7894