PT  - JOURNAL ARTICLE
AU  - David A. Schneider
AU  - Mike Perrone
AU  - James J. Galligan
TI  - Nicotinic Acetylcholine Receptors at Sites of Neurotransmitter Release to the Guinea Pig Intestinal Circular Muscle
DP  - 2000 Jul 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 363--369
VI  - 294
IP  - 1
4099  - http://jpet.aspetjournals.org/content/294/1/363.short
4100  - http://jpet.aspetjournals.org/content/294/1/363.full
SO  - J Pharmacol Exp Ther2000 Jul 01; 294
AB  - Experiments were designed to test the hypothesis that nicotinic acetylcholine receptors (nAChRs) are present at sites of neurotransmission to the guinea pig ileum circular smooth muscle. Circular smooth muscle preparations, from which the myenteric plexus had been removed (circular muscle-axon preparation), were used for this purpose. Nicotine and dimethylphenyl piperazinium iodide (10–100 μM) induced contraction of the circular smooth muscle. Agonist-induced contraction was inhibited by 1 μM scopolamine and abolished in the combined presence of 1 μM scopolamine and 0.3 μM CP 96,345-01, a neurokinin-1 receptor antagonist. Contractions induced by electric field stimulation (30 pulses, 0.5 ms, 70 V, 10 Hz) were abolished by 0.3 μM tetrodotoxin (TTX); in contrast, agonist-induced contraction was attenuated but not abolished by 0.3 μM TTX. Mecamylamine (3 or 30 μM), an nAChR antagonist, blocked agonist-induced contractions. Frequency-response curves for both “ON” and “OFF” electric field stimulation contractions were abolished by the combined presence of 1 μM scopolamine and 0.3 μM CP 96,345-01 or by 0.3 μM TTX. At stimulation frequencies greater than 2 Hz, the ON contraction was increased in the presence of 100 μM nitro-l-arginine. Mecamylamine (3 μM) was used to block the stimulatory prejunctional nAChRs located near sites of neurotransmitter release to the circular smooth muscle; however, ON and OFF contractions were not affected by mecamylamine. Although the prejunctional nAChRs are not targets for endogenously released acetylcholine under the conditions tested here, these receptors may be targets for the development of new prokinetic agents. The American Society for Pharmacology and Experimental Therapeutics