Effect of extracellular calcium on the additive effect of theophylline on the cardiac response to catecholamine
DOI:
https://doi.org/10.22377/ijgp.v2i4.4Abstract
At diff erent extracellular calcium concentrations, the positive inotropic eff ect of isoproterenol and isoproterenol in combinationwith theophylline, a phosphodiesterase inhibitor have been evaluated in the isolated frog heart and the isolated guinea pig left atria to investigate whether extracellular calcium produces any eff ect on the additive eff ect of the theophylline on the cardiac response to catecholamine.
Cumulative dose response study of isoproterenol and isoproterenol in presence of theophylline at diff erent extracellular calcium concentration was performed. Th e study revealed an increase in additive eff ect of theophylline on the cardiac response to catecholamine with increase in extracellular calcium concentration, but increase in extracellular calcium concentration decreased the myocardial
responsiveness to additive eff ect of theophylline and isoproterenol combination. Th e mechanism of positive inotropic eff ect of isoproterenol and in combination with theophylline involves increase in intracellular CAMP by diff erent pathways and extracellular calcium produces positive inotropic eff ect by initiating the interaction between the contractile proteins actin and myosin.The study revealed that an increase in the concentration of extracellular calcium increased the additive eff ect of theophylline and isoproterenol combination, but a decrease in the myocardial responsiveness was observed.
Key words: Additive eff ect, cAMP, isoproterenol, positive inotropic eff ect, theophylline and calcium
Downloads
References
Goodman and Gilman’s ‘The Pharmacological basis of Therapeutics’
th ed. New York: McGraw Hill Medical Publishing Division;
p. 218.
Katz AM. Role of contractile proteins and sarcoplasmic reticulum
in the response of the heart to catecholamine: A historical review.
Adv Cyclic Nucleotide Res II 1979. p. 303-43.
Brodde OE, Hora N, Zerkowaski HR, Rohm N. Human cardiac
beta-adrenoeptors: Both beta-1 and beta-2 adrenoceptors are
functionally coupled to the adenyl cyclase in right atrium. J
Cardiovas Pharmacol 1984;6:1184-91.
Wetzel B, Haul N, New cardiotonic agents: Promising approach for
treatment of heart failure. Trends Pharmacol Sci 1988;9:166-70.
Huxely AI, Simmons RM. Proposed mechanism of force generation
in striated muscle. Nature 1971;233:533-8.
Schmitz W, von der Leyen H, Meyer W, Neumann J, Scholz H.
Phosphodiesterase inhibition and positive inotropic eff ects. J
Cardiovasc Pharmacol 1989;14:S11-4.
Dhalla NS, Anand-Srivastava MB, Tuna BS, Khandelwal RL.
Solublization of calcium dependent adenosine triphosphate from
rat heart sarcolemma. J Mol Cell Cardiol 1981;13:413-23.
Langer GA. Events at the cardiac sarcolemmal localization
and movement of contractile dependent calcium. Fed Proc
;35:1274-8. Source of Support: Nil, Confl ict of Interest: None declared.
Shamkuwar, et al.: Cardiac response to calcium and theophylline
Marban E, Rink TG, Tsien RW, Tsien RY. Free calcium in heart
muscle at rest and during contraction measured with calcium
sensitive microelectrodes. Nature 1980;286:845-50.
Chenoweth MB, Koelle ES, An isolated heart perfusion system
adapted to the determination of nongaseous metabolites. J Lab
Clin Med 1946;31:600-8.
Tortora GJ, Grabowaski SR, Principles of anatomy and Physiology,
th ed. New York: Harper Collins College Publishers; 1996. p.
-8.
Jaime NP, Willson AR. Wilson and Gisvolds Textbook of Organic,
Medicinal and Pharmaceutical Chemistry, 10th ed. New York:
Lippincott Raven Publishers; 1998. p. 482-4.
Tsein RW. Cyclic AMP and contractile activity in heart. Adv Cyclic
Nucleotide Res 1977;8:365-420.
Beavo JA, Reifsydner DH. Primary functions of cyclic nucleotide
phosphodiesterase isoenzymes and design of selective inhibitors.
Trends Pharmacol Sci 1990;199:150-5.
Lefk owitz RJ, Staddel JM, Caron MG. Adenyl cyclase coupled
beta-adrenergic receptors. Ann Rev Biochem 1983;52:86-159.
Ronald EW, James AB. Comprehensive medicinal chemistry. Vol.
New York: Permagoan Press; 1991. p. 501-10.
