Insulin Regulates Neuronal M2 Muscarinic Receptor Function in the Ileum of Diabetic Rats

Coulson, Fiona R., Jacoby, David B. and Fryer, Allison D. (2004) Insulin Regulates Neuronal M2 Muscarinic Receptor Function in the Ileum of Diabetic Rats. The Journal of Pharmacology and Experimental Therapeutics, 308 2: 760-766. doi:10.1124/jpet.103.057570


Author Coulson, Fiona R.
Jacoby, David B.
Fryer, Allison D.
Title Insulin Regulates Neuronal M2 Muscarinic Receptor Function in the Ileum of Diabetic Rats
Journal name The Journal of Pharmacology and Experimental Therapeutics   Check publisher's open access policy
ISSN 0022-3565
Publication date 2004-02
Sub-type Article (original research)
DOI 10.1124/jpet.103.057570
Volume 308
Issue 2
Start page 760
End page 766
Total pages 6
Place of publication Bethesda, MD, USA
Publisher American Society for Pharmacology and Experimental Therapeutics
Language eng
Subject 1115 Pharmacology and Pharmaceutical Sciences
Formatted abstract
Acetylcholine release from cholinergic nerves in the gastrointestinal tract is limited by neuronal M2 muscarinic receptors. In diabetic animals, M2 muscarinic receptor function in the ileum is increased, leading to decreased acetylcholine release and smooth muscle contraction in response to nerve stimulation. The mechanisms responsible for increased M2 muscarinic receptor function are unknown but may contribute to the gastrointestinal dysmotility that occurs frequently in diabetics. In this study, we investigated whether insulin modulates M2 muscarinic receptor function in the gastrointestinal tract of diabetic rats. M2 muscarinic receptor function was tested by measuring the ability of an agonist, pilocarpine, to inhibit and an antagonist, methoctramine, to potentiate electrical field stimulation (EFS)-induced contraction of ileum in vitro. Insulin administration (0.2, 0.6, and 2 U s.c. daily for 7 days) reversed the diabetes-induced increase in M2 muscarinic receptor function and restored normal contractions to EFS. Insulin had no effect on the function of postjunctional M3 muscarinic receptors, determined by measuring contractile responses to acetylcholine. These data suggest that insulin tonically inhibits neuronal M2 muscarinic receptors. Thus, loss of insulin removes this inhibition and increases M2 muscarinic receptor function leading to decreased acetylcholine release and contraction to EFS. In nondiabetic rats, there was a trend that higher insulin doses (0.6 and 2 U) increased M2 muscarinic receptor function, suggesting a bell-shaped concentration-response relationship for insulin. In conclusion, lack of insulin or excess insulin increases M2 muscarinic receptor function in rat ileum. This mechanism may contribute to decreased acetylcholine release in the gastrointestinal tract of diabetics, resulting in dysmotility.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Tue, 11 Apr 2006, 02:10:40 EST