Abstract
On the isolated rabbit papillary muscle experiments were carried out to determine whether the positive inotropic effects mediated by alpha- and by beta- adrenoceptors are brought about by different mechanisms or not.--For this reason the influence of temperature and the effect of the calcium antagonist D600 on the responses to phenylephrine and to isoprenaline were compared. 1. The maximal inotropic effects of phenylephrine, isoprenaline and calcium were not affected by raising the temperature of the organ bath from 37 degrees to 42 degrees C, wheras the basal developed tension of the muscle was significantly decreased. 2. The dose-response curve for phenylephrine was markedly shifted to the right by raising the temperature (pD2=0.89), while that for isoprenaline was also shifted to the right, but to a lesser extent (pD2=0.23). 3. In the presence of 1.5 times 10-8 M pindolol the shift of the dose-response curve for phenylephrine induced by elevation of temperature was more prominent (pD2=1,91), whereas phentolamine (3 times 10-6 M) inhibited the temperature-induced shift. 4. The positive inotropic effect of phenylephrine--mediated by alpha-adrenoceptors under blockade of beta-adrenoceptors by 1.5 times 10-8 M pindolol--was markedly depressed by D600 (10-7 and 3 times 10-7 M): the dose-response curve was shifted to the right ant the maximal response was depressed. On the other hand, the positive inotropic effect of isoprenaline--mediated by beta-adrenoceptors--was affected to a lesser extent by D600 and the maximal response was not changed. It indicates that the stimulation of alpha- adrenoceptors in the rabbit papillary muscle induces a positive inotropic response through a biochemical process different from that caused via beta- adrenoceptors, i. e., stimulation of alpha- adrenoceptors may increase the intracellular calcium level mainly by changing the transmembrane calcium flux.
MeSH Terms
Animals
Calcium/antagonists & inhibitors
Dose-Response Relationship, Drug
Electric Stimulation
In Vitro Techniques
Isoproterenol/pharmacology
Papillary Muscles/drug effects,physiology
Perfusion
Phentolamine/pharmacology
Phenylephrine/pharmacology
Pindolol/pharmacology
Rabbits
Receptors, Adrenergic
Stimulation, Chemical
Temperature
Verapamil/analysis
Chemicals
Receptors, Adrenergic
Phenylephrine
Pindolol
Verapamil
Isoproterenol
Calcium
Phentolamine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Endoh M
Wagner J
Schümann H J
References (23)
23 references, click to expand
-
Alpha sympathomimetic inhibition of adrenergic and cholinergic transmission in the rabbit heart.
Naunyn Schmiedebergs Arch Pharmacol. 1972;274(1):18-45
PMID: 4403611
-
Calcium transport in isolated guinea-pig atria during metabolic inhibition.
Biochim Biophys Acta. 1967 Sep 9;135(4):701-9
PMID: 6057654
-
Blockade of the cardiac action of phenylephrine by bretylium or cocaine.
J Pharmacol Exp Ther. 1970 Apr;172(2):274-81
PMID: 5441156
-
Stimulation by phenylephrine of adrenergic alpha- and beta-receptors in the isolated perfused rabbit heart.
Naunyn Schmiedebergs Arch Pharmacol. 1974;282(3):307-10
PMID: 4277020
-
Inhibition of cyclic-3',5'-nucleotide-phosphodiesterase as a possible mode of action of papaverine and similarly acting drugs.
Naunyn Schmiedebergs Arch Pharmakol. 1970;267(2):189-94
PMID: 4320455
-
The effect of noradrenaline on the calcium uptake of the sarcoplasmic reticulum.
Cardiovasc Res. 1969 Apr;3(2):113-7
PMID: 5821041
-
Myocardial alpha adrenergic receptors and their role in the production of a positive inotropic effect by sympathomimetic agents.
J Pharmacol Exp Ther. 1968 Jan;159(1):82-90
PMID: 4384517
-
Cyclic AMP and calcium uptake of the sarcoplasmic reticulum in relation to increased rate of relaxation under the influence of catecholamines.
Cardiovasc Res. 1970 Apr;4(2):194-200
PMID: 4315947
-
Calcium flux and contractility in guinea pig atria.
J Gen Physiol. 1962 Jan;45:371-94
PMID: 14007471
-
Proceedings: Beta-and-or alpha-adrenoceptors in the ventricular muscle of the rabbit?
Naunyn Schmiedebergs Arch Pharmacol. 1974;282(Suppl):suppl 282:R18
PMID: 4276538
-
Mechanisms of calcium accumulation and transport in cardiac relaxing system (sarcoplasmic reticulum membranes): effects of Verapamil, D-600, X537A and A23187.
J Mol Cell Cardiol. 1972 Dec;4(6):681-7
PMID: 4652932
-
[Problems of therapeutic increase of contractility in hypothermia of the heart].
Klin Wochenschr. 1970 Aug 1;48(15):935-8
PMID: 5519311
-
Characterization of the adrenoceptors mediating the positive ino- and chronotropic effect of phenylephrine on isolated atria from guinea pigs and rabbits by means of adrenolytic drugs.
Naunyn Schmiedebergs Arch Pharmacol. 1974;282(3):295-306
PMID: 4152593
-
Interactions between sympathomimetic amines and blocking agents on the rat ventricle strip.
Arch Int Pharmacodyn Ther. 1966 Apr;160(2):379-89
PMID: 4380923
-
THE INFLUENCE OF THE INTERVAL BETWEEN BEATS ON MYOCARDIAL CONTRACTILITY.
Pharmacol Rev. 1963 Sep;15:601-52
PMID: 14064358
-
Changes of the beta-receptor binding sites of the rabbit ileum under the influence of high temperature.
Experientia. 1973;29(7):830-2
PMID: 4724717
-
Influence of the metabolic state on the action of phenylephrine on rabbit ileum, guinea-pig vas deferens and atrium.
Naunyn Schmiedebergs Arch Pharmacol. 1973;276(1):63-70
PMID: 4266251
-
Positive inotropic effects of phenylephrine in the isolated rabbit papillary muscle mediated both by alpha- and beta-adrenoceptors.
Naunyn Schmiedebergs Arch Pharmacol. 1974;284(2):133-48
PMID: 4153003
-
Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters.
Arch Int Pharmacodyn Ther. 1963;143:299-330
PMID: 13996119
-
Sensitivity changes of adrenergic -receptors of isolated ileum and trachea preparations induced by alteration of temperature.
Arch Int Pharmacodyn Ther. 1972 Jun;197(2):290-300
PMID: 4402301
-
Influence of temperature on the sensitivity of the -receptors and the contractility of guinea-pig atrium.
Naunyn Schmiedebergs Arch Pharmacol. 1972;275(1):95-104
PMID: 4404649
-
[Physiology and pharmacology of sodium, potassium, and calcium movements across the membrane].
Arzneimittelforschung. 1972 Dec;22(12):2019-28
PMID: 4196671
-
Characterization of -adrenoceptors in the myocardium.
Br J Pharmacol. 1973 May;48(1):132-8
PMID: 4146762