PT  - JOURNAL ARTICLE
AU  - HONIG, CARL R.
AU  - REDDY, Y. SURENDRANATH
TI  - EFFECT OF CATECHOLAMINE ANALOGS ON CONTROL OF ACTOMYOSIN BY NATIVE TROPOMYOSIN AND CALCIUM; THE NATURE OF THE NEGATIVE INOTROPIC RECEPTOR
DP  - 1973 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 330--338
VI  - 184
IP  - 2
4099  - http://jpet.aspetjournals.org/content/184/2/330.short
4100  - http://jpet.aspetjournals.org/content/184/2/330.full
SO  - J Pharmacol Exp Ther1973 Feb 01; 184
AB  - Catecholamine analogs increase the amount of Ca required to activate the adenosine triphosphatase (ATPase) of cardiac myosin B but do not change the maximum rate of adenosine triphosphate hydrolysis attained at high Ca concentrations. Data indicate that catecholamine analogs are competitive inhibitors which decrease the affinity of myosin B for Ca. At the pCa at which inhibition is maximal, 5 x 10-4 M dichloroisoproterenol or propranolol halve ATPase activity. Similar results were obtained with skeletal myosin B, but threshold was 50-fold higher and extent of inhibition was smaller. If native tropomyosin is removed from cardiac myosin B, responsiveness to Ca and catecholamine analogs is lost. Replacement of freshly isolated native tropomyosin restores responsiveness to both agents. Aged native tropomyosin restores Ca control but not responsiveness to drugs, indicating that the negative inotropic receptor is not the Ca binding site per se. Of the various components of native tropomyosin, the Ca-binding moiety is essential but not sufficient. We conclude that the functional receptor is the entire native tropomyosin complex. Discussion considers the interaction of intracellular receptors in determining the magnitude and time course of tension in vivo. © 1973 by The Williams & Wilkins Co.