Nicotinic acetylcholine receptors at sites of neurotransmitter release to the guinea pig intestinal circular muscle.
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 microM) induced contraction of the circular smooth muscle. Agonist-induced contraction was inhibited by 1 microM scopolamine and abolished in the combined presence of 1 microM scopolamine and 0. 3 microM 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 microM tetrodotoxin (TTX); in contrast, agonist-induced contraction was attenuated but not abolished by 0.3 microM TTX. Mecamylamine (3 or 30 microM), 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 microM scopolamine and 0.3 microM CP 96,345-01 or by 0.3 microM TTX. At stimulation frequencies greater than 2 Hz, the ON contraction was increased in the presence of 100 microM nitro-L-arginine. Mecamylamine (3 microM) 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.
Schneider
D A
DA
Department of Pharmacology and Toxicology and the Neuroscience Program, Michigan State University, East Lansing, Michigan, USA. das@vetmed.wsu.edu
Perrone
M
M
Galligan
J J
JJ
D000818:Animals; D001369:Axons / Q000502:physiology*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation*; D008297:Male; D009046:Motor Neurons / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000294:innervation*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000032:analysis*; D013779:Tetrodotoxin / Q000494:pharmacology
D018377:Neurotransmitter Agents; D011978:Receptors, Nicotinic; D013779:Tetrodotoxin; D004246:Dimethylphenylpiperazinium Iodide