Distribution of muscarinic receptor subtypes in rat small intestine.
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.
Stadelmann
A M
AM
Department of Medicine, Zablocki VA Medical Center, Milwaukee, Wisconsin, 53295, USA.
Walgenbach-Telford
S
S
Telford
G L
GL
Koch
T R
TR
D000818:Animals; D001667:Binding, Competitive; D003959:Diamines / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000502:physiology; D007421:Intestine, Small / Q000294:innervation / Q000378:metabolism* / Q000637:transplantation*; D007700:Kinetics; D018727:Muscarinic Antagonists / Q000378:metabolism; D009130:Muscle, Smooth / Q000294:innervation / Q000378:metabolism; D010890:Pirenzepine / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011869:Radioligand Assay; D051381:Rats; D011917:Rats, Inbred Lew; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000145:classification* / Q000378:metabolism*; D014018:Tissue Distribution; D014185:Transplantation, Isogeneic
D003959:Diamines; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D010890:Pirenzepine; C054938:methoctramine