5-Hydroxytryptamine and atropine inhibit nicotinic receptors in submucosal neurons.
The whole-cell recording technique was used to investigate the pharmacological properties of acetylcholine-activated ion channels of cultured submucosal neurons from guinea-pig small intestine. Acetylcholine induced whole-cell membrane currents (I(ACh)) in a concentration-dependent manner (EC(50)=79 microM). I(ACh) exhibited strong inward rectification, had a reversal potential of +19+/-2 mV (Na(+) outside, Cs(+) inside), was reversibly inhibited in a concentration-dependent manner by hexamethonium (EC(50)=5 microM) and atropine (EC(50)=1.6 microM), and was unaffected by alpha-bungarotoxin (30 nM). Atropine was less potent in inhibiting the currents induced by 30 microM acetylcholine than those induced by 1 mM acetylcholine. I(ACh) was mimicked by the current induced by nicotine (I(Nic); EC(50)=52 microM). I(Nic) was also blocked by atropine (EC(50)=1.7 microM) and hexamethonium (EC(50)=3.6 microM). 5-Hydroxytryptamine (5-HT) also inhibited I(ACh) in a concentration-dependent manner (EC(50)=180 microM) in the experiments carried out in the presence of a 5-HT(3) receptor antagonist. 5-HT had a similar inhibitory effect after the desensitization of 5-HT(3) receptors or in neurons with relative small 5-HT(3)-mediated currents. The inhibitory actions of hexamethonium, atropine, and 5-HT on I(ACh) were voltage-dependent. Thus, inhibition was significantly smaller for outward currents (recorded at +40 mV) than for inward currents (recorded at -60 mV). Our observations indicate that the I(ACh) of submucosal neurons are mediated by activation of nicotinic channels, which are blocked by atropine, 5-HT, and hexamethonium. The possibility that one of the 5-HT roles in the gastrointestinal tract might be to directly modulate nicotinic channels is discussed.
Barajas-López
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Department of Anatomy and Cell Biology, Queen's University, 9th Floor Botterell Hall, Kingston, Ontario, Canada K7L3N6. BARAJASC@meds.queensu.ca
Karanjia
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Espinosa-Luna
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D018678:Cholinergic Agents / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005731:Ganglionic Stimulants / Q000494:pharmacology; D006168:Guinea Pigs; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D007583:Jejunum / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D013368:Submucous Plexus / Q000187:drug effects / Q000502:physiology
D018678:Cholinergic Agents; D016166:Free Radical Scavengers; D005731:Ganglionic Stimulants; D007473:Ion Channels; D018727:Muscarinic Antagonists; D011978:Receptors, Nicotinic; D012701:Serotonin; D009538:Nicotine; D001285:Atropine; D000109:Acetylcholine