ON THE SITE OF ACTION OF NICOTINE IN FROG RECTUS ABDOMINIS MUSCLE

¹ Departments of Pharmacology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia and University of Texas Southwestern Medical School, Dallas, Texas

Experiments were designed to elicit information about the cellular site of action of nicotine in frog rectus abdominis muscle. Nicotine (6.16 and 61.6 µM) increased muscle ⁴⁵Ca retention after a subsequent 120-minute washout, decreased total Ca⁺⁺ content and did not alter ⁴⁵Ca loss when added during the slow component phase of the washout. Increasing pH from 6.80 to 9.40 increased nicotine-induced ⁴⁵Ca retention and decreased the rate of development (but not the magnitude) of the contractile response. Procaine (3.67 mM), high K⁺ (80 mM) and d-tubocurarine (25 µM) but not acetylcholine (ACh 2.3 µM) blocked contractions and increased ⁴⁵Ca retention induced by nicotine, whereas nicotine blocked contractions elicited by ACh but not those obtained with high K⁺. Hemicholinium-3 partially inhibited contractions and the increased ⁴⁵Ca retention elicited by nicotine but did not affect similar actions of ACh. These results indicate that nicotine 1) acts at receptors at the neuromuscular junction and only a portion of these may be ACh receptors, 2) is active in both ionized and nonionized molecular forms and 3) does not exert these actions at sites beyond the neuromuscular junction. The varied responses obtained with either the ionized or nonionized forms of nicotine occur at similar extracellular concentrations. The importance of each of these stimulatory mechanisms in the evaluation of actions of nicotinie agents on frog rectus abdominis muscle is uncertain.