Mechanism of action of nicotine in isolated iris sphincter preparations of rabbit.

1. Nicotine produced a transient contraction of rabbit isolated iris sphincter muscle, a parasympathetic ganglion-free tissue. The response to nicotine was antagonized by hexamethonium, but was insensitive to tetrodotoxin (TTX). While single treatments with atropine, capsaicin or [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (rpwwL-SP) partially blocked the response, combined treatment abolished it. 2. Chronic treatment of animals with nicotine added to the drinking water (about 12 mg kg-1 per day) had no effect on the responsiveness to nicotine or the pharmacological properties of nicotine-induced contraction. 3. These results suggest that acetylcholine and tachykinin(s) released via sodium channel-independent mechanisms from nerve terminals of parasympathetic and primary sensory nerves, respectively, are involved in the nicotine-induced contractile response.