Adrenergic drug-receptor interaction in the presence of strontium (Sr++) in mammalian myocardium.
The specificity of Ca++ for the interaction of beta adrenergic agonists with their receptors in rabbit right atrial muscle was evaluated. This was accomplished by substituting Ca++ by an equimolar concentration of Sr++. Dose-response curves which demonstrate the effect of norepinephrine and isoproterenol on the rate of electrical activity in the presence of Ca++ or Sr++ were made. In addition, the antagonistic action of propranolol (1 X 10(-7) M) in a Ca++-containing or Sr++-containing medium was determined. The results clearly demonstrate that Sr++ can effectively substitute for Ca++ in maintaining electrical and mechanical activity in cardiac muscle. Also, norepinephrine and isoproterenol can increase the rate of electrical activity in a Ca++ or Sr++-containing medium. This effect of these beta agonists is mediated through the beta-receptors since propranolol effectively blocked their action. It appears that Ca++ per se is not required for beta agonist or antagonist-receptor interaction in cardiac muscle. The results are discussed in relation to the dependency on extracellular Ca++ for beta agonists to cause a change in the rate of electrical activity after receptor occupancy.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects*; D013324:Strontium / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011941:Receptors, Adrenergic; D003035:Cobalt; D008345:Manganese; D007545:Isoproterenol; D002118:Calcium; D009638:Norepinephrine; D013324:Strontium