RT Journal Article
SR Electronic
T1 SITES OF ACTION OF LILLY 18947 IN SKELETAL MUSCLE
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 373
OP 384
VO 186
IS 2
A1 G. SUAREZ-KURTZ
A1 F. J. R. PAUMGARTTEN
YR 1973
UL http://jpet.aspetjournals.org/content/186/2/373.abstract
AB 2,4-Dichloro-6-phenylphenoxyethyl diethylamine hydrobromide (Lilly 18947, LY), in a concentration of 0.1 to 1.0 mM, induced transient contracture of frog sartorius muscle. There was no marked change in resting potential, and contractures could be elicited in depolarized muscles. The LY contracture was markedly depressed by removal of external Ca, by La, and by previous elicitation of a quinine contracture. It was potentiated in Cl-free media. The rate of rise and peak tension of the LY contracture decreased with repeated applications. This was prevented by caffeine. LY increased 45Ca-efflux from the sartorius muscle. Procaine blocked the LY-induced tension and 44Ca-effiux. LY abolished spike and twitch of the electrically driven sartorius muscle and inhibited K contractures. In contrast, LY potentiated quinine- and caffeine-induced contractures. The potentiation of caffeine was not affected by procedures which depress the LY contracture. Ca uptake by rabbit muscle microsomes (in the presence of adenosine triphosphate and oxalate) was inhibited by LY. The effects of LY and caffeine in this preparation were synergistic. The results suggest that LY releases Ca from sites which readily equilibrate with the external medium and prevents Ca sequestration by the sarcoplasmic reticulum. These actions could account for the LY-induced contracture and potentiation of caffeine and quinine. Blockade by LY of contractions elicited by membrane depolarization can be attributed to depression of membrane excitability by the drug. © 1973 by The Williams & Wilkins Co.