Depressed smooth muscle contractility after massive intestinal resection in rat: Role of alterations in muscarinic receptor status or source of calcium for excitation-contraction coupling

Following massive intestinal resection (removal of 75% of the mid-jejunoileum) in the rat, there is a significant reduction in the in vitro tonic contractile response of the remaining jejunal circular smooth muscle in response to stimulation with the muscarinic agonist bethanechol. The aim of these experiments was to determine if this alteration is specific to muscarinic excitation and occurs as a result of changes in the source and availability of calcium required for excitation-contraction coupling, or reflects changes in muscarinic receptor number and (or) affinity. The contractile response of proximal jejunal circular muscle strips from sham-operated and resected rats was studied in vitro in response to electrical field stimulation, serotonin, and bethanechol, the latter under conditions where extracellular calcium was absent or entry was excluded. In contrast with the significant reduction in tonic contractile response to muscarinic excitation of tissues from resected animals, there was an equivalent or enhanced response of these tissues to electrical field stimulation and serotonin, respectively. While sham-operated and resected groups showed similar dependency upon or availability of intracellular and extracellular calcium, the data indicate distinct pathways of calcium mobilization for tonic versus phasic contractile activity. Muscarinic receptor number and affinity were assessed by 1-quinuclidinyl[phenyl-4-H-3]benzilate ([H-3]QNB) binding to isolated smooth muscle cells and showed a significant increase in B-max, with no change in K-d after resection. Thus, the reduced contractility of the circular muscle of the remnant jejunum after massive intestinal resection is a specific event associated with muscarinic receptor activation, but it is not the result of either an alteration in the source or availability of calcium required for excitation-contraction coupling or a reduction in the number and (or) affinity of muscarinic receptors.