Faculty Collaboration Database

Distribution of muscarinic receptor subtypes in rat small intestine. J Surg Res 1998 Dec;80(2):320-5

Date

01/08/1999

Pubmed ID

9878332

DOI

10.1006/jsre.1998.5431

Scopus ID

2-s2.0-0032446908 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

Despite its great promise, small intestinal transplantation in some patients is complicated by difficult postoperative management. The reasons for this are complex. In a rat model of small intestinal transplantation, frequencies of migrating myoelectric complexes during fasting are reduced in ileal isografts and muscarinic receptor density is decreased. We hypothesized that the distribution of muscarinic 1 receptors localized to enteric neurons is altered after small intestinal transplantation. Distal small intestine was orthotopically transplanted in Lewis-to-Lewis donor-recipient combinations. At 3 months, transplanted and normal ileum was obtained to prepare membrane fractions. [N-methyl-3H]Scopolamine served as ligand, while scopolamine methylbromide, pirenzepine, and methoctramine were used in competitive homologous and heterologous displacement experiments. Receptor subtype models were examined by nonlinear regression analysis. In normal and transplanted ileum, heterologous displacement was consistent with three site models (P < 0.05). In normals, the muscarinic 1 receptor subtype was most abundant, with a relative distribution of 69 to 78%. There was a relative distribution of 13 to 16% for muscarinic 3 receptor subtype. After transplantation, the muscarinic 1 subtype decreased to a mean of 45% but the muscarinic 3 subtype increased to a mean of 42%. Using pirenzepine, mean pKD values were not different between the two groups. It is concluded that the decrease in muscarinic 1 receptor subtype after transplantation could be related to neuronal cell loss or to downregulation of the expression of muscarinic 1 receptors. The results did not support defective posttranslational processing of receptor proteins.

Author List

Stadelmann AM, Walgenbach-Telford S, Telford GL, Koch TR

MESH terms used to index this publication - Major topics in bold

Animals
Binding, Competitive
Diamines
Gastrointestinal Motility
Intestine, Small
Kinetics
Muscarinic Antagonists
Muscle, Smooth
Pirenzepine
Protein Processing, Post-Translational
Radioligand Assay
Rats
Rats, Inbred Lew
Receptor, Muscarinic M1
Receptor, Muscarinic M2
Receptor, Muscarinic M3
Receptors, Muscarinic
Tissue Distribution
Transplantation, Isogeneic