Document Detail

Cholinergic neurons and muscarinic receptors regulate anion secretion in pig distal jejunum.
MedLine Citation:
PMID:  2055245     Owner:  NLM     Status:  MEDLINE    
The neurotransmitter acetylcholine is thought to modulate epithelial ion transport in the mammalian small intestine. In this study, the non-selective acetylcholine agonist, carbachol, produced rapid changes in short-circuit current (Isc), an electrical measure of active anion secretion, across isolated sheets of the distal jejunal mucosa-submucosa from swine. The potency of carbachol in elevating Isc was decreased 26-fold in the presence of 10 nM atropine, but remained unchanged by 1-100 microM hexamethonium or 0.1 microM tetrodotoxin. The acetylcholine antagonists produced little or no decrease in spontaneous Isc, whereas tetrodotoxin decreased Isc by 54 microA/cm2. [3H]Quinuclidinyl benzilate (QNB), a muscarinic acetylcholine receptor blocker, bound to a single species of sites within the mucosa-submucosa with a KD = 38 pM and Bmax = 94 fmol/mg protein. Selective muscarinic acetylcholine receptor blockers competed with [3H]QNB for this site with a rank order of affinity indicative of an interaction with a M3-muscarinic acetylcholine receptor. Specific [3H]QNB binding sites were autoradiographically localized in the jejunal wall to the epithelium, submucosa and muscularis propria. Transmural electrical stimulation (3-600 pulses/10 s, 0.5 ms, 60 V) of the mucosa-submucosa produced increases in Isc which were dependent upon the number of impulses delivered and did not undergo tachyphylaxis upon repeated stimulation. Responses to electrical transmural stimulation were inhibited by atropine and hexamethonium, as well as the respective neuronal Na+ and Ca2+ channel blockers tetrodotoxin and omega-conotoxin GVIA, suggesting that electrical transmural stimulation depolarizes submucosal cholinergic neurons which terminate on ion-transporting epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
R Chandan; K R Hildebrand; V S Seybold; G Soldani; D R Brown
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  European journal of pharmacology     Volume:  193     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1991 Feb 
Date Detail:
Created Date:  1991-07-31     Completed Date:  1991-07-31     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  265-73     Citation Subset:  IM    
University of Minnesota, Department of Veterinary Biology (Pharmacology Section), College of Veterinary Medicine, St. Paul, MN 55108.
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MeSH Terms
Acetylcholine / physiology
Anions / metabolism
Bicarbonates / metabolism*
Carbachol / metabolism,  pharmacology
Chlorides / metabolism*
Dose-Response Relationship, Drug
Electric Stimulation
Intestinal Mucosa / secretion
Jejunum / innervation,  metabolism,  secretion*
Neurons / physiology*,  ultrastructure
Quinuclidinyl Benzilate / metabolism
Receptors, Muscarinic / metabolism,  physiology*
Grant Support
Reg. No./Substance:
0/Anions; 0/Bicarbonates; 0/Chlorides; 0/Receptors, Muscarinic; 51-83-2/Carbachol; 51-84-3/Acetylcholine; 6581-06-2/Quinuclidinyl Benzilate

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