The Antagonism of Acetylcholine and of Quaternary Ammonium Salts

Clark, A. J.; Raventós, J.

doi:10.1113/expphysiol.1937.sp000729

Cited by 50 publications

(28 citation statements)

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“…3). The pA30 of atropine in the guinea-pig atrium (8.4) was similar to that in the frog atrium (8.3), which has been calculated from the results of Clark & Raventos (1937).…”

Section: Resultsmentioning

confidence: 81%

Antagonism of Acetylcholine by Adrenaline Antagonists

Benfey

Grillo

1963

British Journal of Pharmacology and Chemotherapy

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Phenoxybenzamine antagonized the inhibitory action of acetylcholine on the guineapig isolated atrium. The antagonism was slow in onset, very slowly reversible, and could be overcome by increased concentrations of acetylcholine. In contrast, atropine inhibited the action of acetylcholine quickly, and the effect disappeared soon after withdrawal. The pAio of phenoxybenzamine (2 hr of contact) was 6.8, and that of atropine (30 min of contact) was 8.4. In the presence of atropine phenoxybenzamine did not exert a slowly reversible antagonism, and the dose-ratio of acetylcholine returned to normal soon after withdrawal of both drugs. Phenoxybenzamine also antagonized acetylcholine in the guinea-pig isolated ileum, but with higher concentrations acetylcholine did not overcome the antagonism. The pAio (60 min of contact) was 6.6. The pAio of chlorpromazine in the atrium (2 hr of contact) and ileum (60 min of contact) was 5.9. Phentolamine, 2-diethylaminomethylbenzo-1,4-dioxan hydrochloride (883 F), and yohimbine antagonized acetylcholine in the atrium and ileum but required higher concentrations than chlorpromazine.

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“…3). The pA30 of atropine in the guinea-pig atrium (8.4) was similar to that in the frog atrium (8.3), which has been calculated from the results of Clark & Raventos (1937).…”

Section: Resultsmentioning

confidence: 81%

Antagonism of Acetylcholine by Adrenaline Antagonists

Benfey

Grillo

1963

British Journal of Pharmacology and Chemotherapy

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“…The method was based on earlier suggestions by Clark and Raventos (1937), according to which the antagonisti c power of a b10cking agent was expressed as "the concentrati on of antagonist which a1tered by a selected proportion (e.g. tenfold) the concentration of an active drug needed to produce a selected effect ll • The negative logarithm of this (molar) concentrati on has been termed pAx' where x is the proportion selected.…”

Section: General Introductionmentioning

confidence: 99%

Transformation of Adrenergic Receptors in the Myocardium

1973

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·ABSTRACTThe present series of experiments provided evidence that the generally accepted distinction between a-and s-adrenergic receptors is not immutable. In frog hearts and rat atria 3H-phenoxybenzamine (3H-POB ) blocked inotropic responses to catecholamines only at temperatures below l7 0 C and potentiated responses ab ove 23 0 C, and considerably more radioactivity was bound to the myocardium at lower temperatures. The converse was true for l4C-propranolol, and the potency of a-and s-adrenergic agonists was shawn to parallel the effectiveness of the blocking agents. Alkylation of a-adrenergic receptors by POB at l4 0 c prevented the appearance of s-adrenergic receptors when the temperature was subsequently raised ta 24 o C.Phentolamine prevented block by 3H-POB and considerably reduced its binding ta the myocardium at low but not at high temperatures. After exposure ta unlabelled POB in the presence of phentolamine at low temperature and thorough washing, exposure to 3H-POB produced a IIpositive label" of the adrenergic receptors, which was localized in a 20,000 9 (ll mitochondrial ll ) and in a IIsoluble protein" fraction. Pretreatment of rats with 6-hydroxydopamine, but not with reserpine, prevented the appearance of oe-adrenergic receptor charac.teristics in left atria at low temperatures; this indicated that adrenergic innervation, but probably not stores of neurotransmitter, is necessary to allow transformation of the receptors. It is suggested that a-and S-adrenergic receptors may be different allosteric conformations of the same molecule.

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“…This should perhaps have been foreseen, since Ravent6s (1937) made passing reference to hexyl-TMA and octyl-TMA producing effects, on the frog heart and rat ileum respectively, which could not be increased by increasing the concentration. In the present experiments The efficacy e can have any positive value; there will presumably be some practical limit, but no theoretical limit can be imposed.…”

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confidence: 99%

“…mate of slope, but it was evident that the increase (2) The (Reuse, 1948) causes an of reducing data about concentration-effect curves effect and an antagonist causes no effect so that to a single figure which is independent of any the activity of a drug of either kind is simply a theory of drug action, and which can therefore be measure of its affinity for the receptoig Accord- (Ravent6s, 1937a and where fractions are involved. Equation 1 appears b; Clark and Ravent6s, 1937 METHODS A guinea-pig (usually weighing 150-200 g.) was killed by a blow on the head and bled. The terminal 3-4 cm.…”

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confidence: 99%