Sixth Gaddum Memorial Lecture National Institute for Medical Research, Mill Hill, January 1977

Langer, S. Z.

doi:10.1111/j.1476-5381.1977.tb07526.x

Cited by 917 publications

(22 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With respect to the mode of delivery of noradrenaline, this approach will more closely resemble the physiological setting, although we are fully aware that with respect to the mechanisms involved this pharmacologically induced release still differs from the physiological conditions where noradrenaline is released upon nerve stimulation. Thus, tyramine-induced release of noradrenaline is not subject to receptor-mediated prejunctional modulation and is independent of the presence of calcium ions in the biophase (Langer 1977).…”

Section: Methodological Considerationsmentioning

confidence: 99%

Influence of adrenoceptor and muscarinic receptor blockade on the cardiovascular effects of exogenous noradrenaline and of endogenous noradrenaline released by infused tyramine

Schäfers¹,

Poller

Pönicke

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

This study aimed firstly to compare the in vivo cardiovascular effects of exogenously administered and of endogenously released noradrenaline; secondly to characterize the adrenoceptors mediating these responses; thirdly to assess the influence of parasympathetic tone on the cardiovascular effects of noradrenaline. In two randomised placebo-controlled studies, healthy, young, male volunteers received intravenous (i.v.) infusions of noradrenaline at six incremental doses of 10-160 ng/kg/min and-in order to release endogenous noradrenaline-tyramine at four incremental doses of 5-20 micrograms/kg/min. Noradrenaline and tyramine were administered in the absence and presence of alpha 1-adrenoceptor blockade with doxazosin (2 mg p.o.), alpha 2-adrenoceptor blockade with yohimbine (15 mg p.o.), selective beta 1-adrenoceptor blockade with bisoprolol (15 mg p.o.) and muscarinic receptor blockade with atropine (1.5 micrograms/kg i.v. loading dose followed by 0.15 microgram/kg/min by i.v. infusion). Vasoconstrictor effects were assessed by measurement of diastolic blood pressure (Pdiast) and myocardial effects by measurement of systolic time intervals, namely the duration of electromechanical systole corrected for heart rate (QS2c). I.v. noradrenaline increased Pdiast (delta max 17 mmHg) and this was nearly completely suppressed by doxazosin but only slightly blunted by yohimbine. Noradrenaline also slightly shortened QS2c (delta max -22 ms), and this was potentiated by both doxazosin and yohimbine and completely blocked by biosprolol. I.v. tyramine reduced Pdiast (delta max -7 mmHg), which was not affected by alpha 1-adrenoceptor blockade, and profoundly shortened QS2c (delta max -104 ms) which was significantly correlated with a marked increase in systolic blood pressure (Psyst) (delta max 57 mmHg). The shortening of QS2c and the rise in Psyst were not influenced by alpha-adrenoceptor blockade but were antagonized by bisoprolol. Atropine potentiated the blood pressure rise and the shortening of QS2c induced by i.v. noradrenaline and converted the fall in Pdiast induced by i.v. tyramine into an increase. Thus the cardiovascular effects of exogenous noradrenaline are mainly characterized by alpha 1-adrenoceptor-mediated vasoconstriction and the actions of endogenous noradrenaline (released by i.v. tyramine) by beta 1-adrenoceptor-mediated positive inotropic effects. The rise in Psyst with i.v. tyramine most likely reflects positive inotropism and not a vascular "pressor' response.

show abstract

Section: Methodological Considerationsmentioning

confidence: 99%

Influence of adrenoceptor and muscarinic receptor blockade on the cardiovascular effects of exogenous noradrenaline and of endogenous noradrenaline released by infused tyramine

Schäfers¹,

Poller

Pönicke

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

show abstract

“…a-Adrenoceptors have been differentiated into pre-(a,) and post-(a,)-synaptic entities (Langer 1974(Langer , 1977Starke & Endo 1976;Berthelsen & Pettinger 1977). Thus prazosin is now considered a n a,-receptor antagonist while yohimbine is considered a preferential a,-receptor antagonist.…”

mentioning

confidence: 97%

Cardiovascular effects of 2-(NN-dimethyl)amino-6,7-dihydroxy-1,2,3,4 tetrahydronaphthalene in pithed rats: differential antagonism by yohimbine and prazosin

Hicks

Cannon

1980

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

“…Postsynaptic a-adrenoceptors are located in the membranes of myocardial or arteriolar cells, whereas presynaptic a-adrenoceptors are situated in the membranes of nerve endings (1). The presence of both classes of receptors in our preparation could be expected from the use of a crude membrane pellet which can contain both cardiac and nerve ending membranes.…”

Section: Discussionmentioning

confidence: 99%

“…This distinction was made possible by labeling a-adrenocept6rs with 3H-DHE in the presence of various aadrenergic antagonists known to interact preferentially with either presynaptic or postsynaptic receptors. We now report the use of a similar binding technique to show the presence of a-adrenoceptors in a rat heart membrane preparation with the properties of presynaptic and postsynaptic receptors whose existence had been suggested by various pharmacological experiments (1,3). This study was facilitated by preliminary observations (not shown) that heart membranes, in contrast to brain membranes, do not possess dopaminergic and serotonergic binding sites, which are also able to interact with 3H-DHE (4,5).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Biochemical evidence for presynaptic and postsynaptic alpha-adrenoceptors in rat heart membranes: positive homotropic cooperativity of presynaptic binding.

Guicheney¹,

Garay²,

Lévy-Marchal³

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

In crude rat cardiac membrane preparations, could be differentiated into two classes of receptors showing similarities with peripheral presynaptic and postsynaptic aadrenoceptors. This distinction was made possible by labeling a-adrenocept6rs with 3H-DHE in the presence of various aadrenergic antagonists known to interact preferentially with either presynaptic or postsynaptic receptors. We now report the use of a similar binding technique to show the presence of a-adrenoceptors in a rat heart membrane preparation with the properties of presynaptic and postsynaptic receptors whose existence had been suggested by various pharmacological experiments (1, 3). This study was facilitated by preliminary observations (not shown) that heart membranes, in contrast to brain membranes, do not possess dopaminergic and serotonergic binding sites, which are also able to interact with 3H-DHE (4,5). This finding allowed us to perform a detailed study of the molecular properties of presynaptic and postsynaptic binding sites.Three important results were obtained in the present investigation. (i) Heart membranes contain an equal or higher amount of presynaptic than of postsynaptic a-adrenoceptors.(ii) Postsynaptic a-adrenoceptors show a high-affinity interaction with 3H-DHE according to the law of mass action. (iii) Interaction of 3H-DHE with presynaptic receptor sites exhibits the characteristics of a markedly positive homotropic cooperativity. This property provides an explanation, at the molecular level, for the mechanism regulating norepinephrine release from nerve endings. MATERIAL AND METHODSExperiments were performed on a crude membrane preparation of rat heart, in order to avoid the possible loss of a-receptors which might result from more extensive purification. Homogenates were prepared by differential centrifugation between 400 and 28,000 X g according to the original method of Williams and Lefkowitz (6). The incubation buffer used for binding studies was 10 mM MgCl2/50 mM Tris-HCI, pH 7.5. 3H-DHE (New England Nuclear; specific activity, 24.1 Ci/ mmol) (0.5-0 nM) and myocardial membranes (400-600 mg) were incubated in glass tubes with and without a high concentration (50 MM) of the unlabeled a-blocker phentolamine, in a final volume of 300 ,l of incubation buffer. Incubations were stopped by diluting 200Wl aliquots with 4 ml of cold (40C) buffer followed by rapid filtration through Whatman GF/C glass fiber filters. Filters were rapidly washed with 15 ml of cold incubation buffer, dried, and assayed for radioactivity in 6 ml of Permafluor solution in a Packard Prias PL Tri-Carb liquid scintillation counter with an efficiency of 42%. Specific binding was taken as the difference between radioactivity measured on the filters in the absence and presence of phentolamine and represented 50-60% of the total binding of 3H-DHE.Addition to the incubation mixture of saturating concentrations of compounds, such as prazosin or ARC 239, which preferentially interact with postsynaptic receptors (A. M. Huchet, P. Mouille, R. Kadat...

show abstract

Sixth Gaddum Memorial Lecture National Institute for Medical Research, Mill Hill, January 1977

Cited by 917 publications

References 89 publications

Influence of adrenoceptor and muscarinic receptor blockade on the cardiovascular effects of exogenous noradrenaline and of endogenous noradrenaline released by infused tyramine

Influence of adrenoceptor and muscarinic receptor blockade on the cardiovascular effects of exogenous noradrenaline and of endogenous noradrenaline released by infused tyramine

Cardiovascular effects of 2-(NN-dimethyl)amino-6,7-dihydroxy-1,2,3,4 tetrahydronaphthalene in pithed rats: differential antagonism by yohimbine and prazosin

Biochemical evidence for presynaptic and postsynaptic alpha-adrenoceptors in rat heart membranes: positive homotropic cooperativity of presynaptic binding.

Contact Info

Product

Resources

About