INFLUENCE OF MECAMYLAMINE ON CONTRACTIONS INDUCED BY DIFFERENT AGONISTS AND ON ROLE OF CALCIUM-IONS IN ISOLATED RABBIT AORTA

Abstract

The exposure of helically cut strips of rabbit aorta to mecamylamine (1 mM) for 5 min blocked the histamine (3.25 .mu.M)-induced contractions completely and reduced those induced by K (25 mM, 68%) without affecting contractions induced by norepinephrine (3.0 .mu.M, NE) or acetylcholine (10 .mu.M). Mecamylamine, alone did not exhibit agonist activity, but it increased the contractile tension of the muscle which was contracted by NE. The responses to NE were either enhanced or not affected by small doses of mecamylamine (1 mM) but were partially blocked by large doses of mecamylamine (10 mM). The antagonism exhibited by mecamylamine in low doses (1 mM) against the above agonists was reversible. The shape of the response to NE on the muscle, which was treated with a high dose of mecamylamine (10 mM) and washed, was significantly different from that of the control. The results are consistent with the following conclusions: mecamylamine in low doses (1 mM) blocks the histamine receptor and therefore the histamine-induced contractions; two molecules of mecamylamine are competitive with 1 molecule of histamine; mecamylamine blocks the K-induced contractions but does not block completely the Ca influx in the K-depolarized muscles and may interfere partially with the utilization of extracellular or loosely bound Ca during K-induced contractions; mecamylamine in high doses (10 mM) partially blocks norepinephrine-induced contractions by affecting firmly bound Ca stores; and procaine antagonizes the effects of NE, histamine and acetylcholine by affecting, at least partially, the firmly bound Ca stores.