Abstract
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.
Footnotes
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Send reprint requests to: Dr. David A. Schneider, Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Program in Neuroscience, P.O. Box 646520, Washington State University, Pullman, WA 99164-6520. E-mail:das{at}vetmed.wsu.edu
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↵1 This work was supported by Grants 1 F32 DK09935-01 and NS33289 and by an American Society of Pharmacology and Experimental Therapeutics Summer Institutional Fellowship awarded to the Department of Pharmacology and Toxicology, Michigan State University (to M.P.).
- Abbreviations:
- ENS
- enteric nervous system
- ACh
- acetylcholine
- nAChR
- nicotinic ACh receptors
- CM-axon
- circular muscle-axon
- TTX
- tetrodotoxin
- DMPP
- dimethyl-phenyl piperazinium iodide
- NK-1
- neurokinin-1
- mAChR
- muscarinic ACh receptor
- EFS
- electric field stimulation
- NLA
- nitro-l-arginine
- Received October 27, 1999.
- Accepted April 5, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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