INHIBITION OF CONTRACTION AND CALCIUM EXCHANGEABILITY IN RAT UTERUS BY LOCAL ANESTHETICS

¹ Division of Physiology, Institute for Muscle Disease, New York, New York, and Department of Pharmacology, State University of New York Downstate Medical Center, Brooklyn, New York

Calcium-induced contractions of isolated rat uteri depolarized with K₂SO₄ are prevented or abolished by local anesthetics, epinephrine or caffcine. Analysis of the Ca²⁺ dose-response relationships in the presence of these inhibitory drugs indicates that local anesthetics act competitively, whereas epinephrine and caffeine act noncompetitively. Time washout of radioactive calcium from rat uteri, by a Ca²⁺-free solution, has a time course which can be broken down into at least three distinct exponential phases. Calcium added after 120 mm of washout (during the slowest exponential phase: t 100-120 min) elicited a 7-fold increase in the rate of Ca⁴⁵ exit from the tissue within the first 5 min. Tetracaine (3.3 mM) decreased the Ca⁴⁵ efflux due to addition of "cold" calcium by about 50%. Epinephrine and caffeine, in sufficient concentration to abolish the contractile response to calcium, were without effect on the exchange of added calcium with tissue Ca⁴⁵. The effect of 0.2 to 0.3 mM tetracaine (80-100% inhibition) on spontaneous contractions of rat uteri in Krebs' solution is rapidly reversed by a 3-fold increase in calcium concentration of the bath. Calcium has a much slower, and almost negligible, antagonistic action vs. epinephrine and caffeine. These results suggest that the action of the local anesthetics on rat uterus in either Krebs' solution or K₂S0₄ depolarizing solution is manifested by an antagonism of Ca²⁺ entry into or through the cell membrane.