The influence of mecamylamine on contractions induced by different agonists and on the role of calcium ions in the isolated rabbit aorta.

The exposure of helically cut strips of rabbit aorta to mecamylamine (1 mM) for 5 minutes blocked the histamine (3.25 muM)-induced contractions completely and reduced those induced by potassium (25mM, 68%) without affecting contractions induced by norepinephrine (3.0 muM, NE) or acetylcholine (10 muM). Mecamylamine, by itself, 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 (20 mM) and washed, was significantly different from that of the control. Our results are consistent with the following conclusions: 1) 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. 2) Mecamylamine blocks the potassium-induced contractions, but does not block completely the calcium influx in the potassium-depolarized muscles. Therefore, it may interfere partially with the utilization of extracellular or loosely bound calcium during potassium-induced contractions. 3) Mecamylamine in high doses (10 mM) partially blocks norepinephrine-induced contractions by affecting firmly bound calcium stores. 4) Procaine antagonizes the effects of NE, histamine and acetylcholine by affecting, at least partially, the firmly bound calcium stores.