Distribution of muscarinic receptor subtypes in rat small intestine

Despite its great promise, small intestinal transplantation in some patient s is complicated by difficult postoperative management, The reasons for thi s are complex. In a rat model of small intestinal transplantation, frequenc ies of migrating myoelectric complexes during fasting are reduced in ileal isografts and muscarinic receptor density is decreased. We hypothesized tha t the distribution of muscarinic 1 receptors localized to enteric neurons i s altered after small intestinal transplantation. Distal small intestine wa s orthotopically transplanted in Lewis-to-Lewis donor-recipient combination s. At 3 months, transplanted and normal ileum was obtained to prepare membr ane fractions. [N-methyl-H-3]Scopolamine served as ligand, while scopolamin e methylbromide, pirenzepine, and methoctramine were used in competitive ho mologous 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, w ith 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 subty pe increased to a mean of 42%. Using pirenzepine, mean pK(D) values were no t different between the two groups. It is concluded that the decrease in mu scarinic 1 receptor subtype after transplantation could be related to neuro nal cell loss or to downregulation of the expression of muscarinic 1 recept ors. The results did not support defective posttranslational processing of receptor-proteins. a (C) 1998 Academic Press.