Intestinal inflammation alters the contractile activity of intestinal smooth muscle. Motility disorders of the gastrointestinal tract are clinically important symptoms, because they are often associated with severe interstitial inflammation. In addition, the motility disorders secondarily induce abnormal growth of the intestinal flora, and the resulting disturbance of this flora aggravates the pathogenesis of mucosal inflammation. This in turn aggravates the intestinal dysmotility; i.e., it is an inflammatory spiral. Therefore, it is important to elucidate the mechanisms involved in the changes in motor function which occur in intestinal inflammation. Recent studies have revealed several molecular mechanisms responsible for the decreased motility which occurs in an inflamed gastrointestinal tract. In the present review, we discuss the functional failure of smooth muscle cells, including changes in the activity of muscarinic receptors, ion channels and the endogenous myosin phosphatase inhibitor CPI-17.
Neuropathic bladder dysfunction results from abnormal development of the spine, spinal cord injuries, or diseases such as diabetics. Patients with neuropathic bladders often require surgical intervention such as bladder reconstruction to improve incontinence and prevent renal damage. Tissue engineering with ex-vivo cultured bladder cells has been suggested as one means for improving bladder function. However, we previously demonstrated that cultured bladder smooth muscle cells (SMCs) derived from neuropathic bladder exhibit and maintain altered pathologic phenotypes in culture. To identify genes that are responsible for the abnormal neuropathic phenotypes specifically elevated cell proliferation, the expression levels of 1,185 genes were compared between cultured SMCs derived from normal and neuropathic bladders using a cDNA array consisting of well-annotated genes. The expression data were analyzed using several methods to identify differentially expressed genes. The resulting sets of differentially expressed genes were examined by pathway analysis to identify the networks that remain abnormal in the culture-stable phenotype of neuopathic SMCs. A total of 18 genes that are differentially expressed between cultured normal and neuropathic bladder SMCs were identified. Of these 17 were up-regulated greater than 2-fold in neuropathic bladder SMCs, six of them along with one gene that was not up-regulated greater than 2-fold in cultured neuropathic bladder SMCs were confirmed and identified by more stringent analysis methods including significance analysis of microarrays, class comparison, and class prediction analyses. The major dysregulated pathways include fibroblast growth factor signaling, PTEN signaling, and integrin signaling. Our results further suggest that altered neuropathic bladder SMC phenotypes is stable in the culture environments and that SMCs derived from diseased bladders may not be appropriate for tissue engineering purpose without modification of pathologically altered genes expression.
Microscopic observation of intramural nerves in the frog esophagus, fixed and stained with OsO4 and ZnI2, revealed that nerve cell bodies and bundles connecting the nerve cell bodies formed loose and irregular networks. The nerve cell bodies were mostly lying singly in the nerve bundles, with occasional observations of two closely linked nerve cell bodies. Isolated circular and longitudinal segments of esophageal muscle were spontaneously rhythmically contractile, with a frequency of 2.2-3.0 per min. This was not altered by tetrodotoxin (TTX). In longitudinal muscle segments, transmurally applied electrical stimulation produced contractile responses which were not inhibited by atropine or guanethidine, but were reduced in amplitude by TTX, suggesting a nonadrenergic-noncholinergic (NANC) excitatory innervation in the esophagus muscle. In circular muscle segments, transmural application of brief electrical stimulation evoked two types of mechanical response: a biphasic response consisting of an initial relaxation and a following contraction (type I) and a contraction alone (type II). These mechanical responses were not modulated by either atropine or guanethidine. In the type I response, TTX abolished the relaxation component, suggesting that this was produced by non-adrenergic non-cholinergic (NANC) inhibitory nerve excitation. In about half of the type II responses, the amplitude of the contraction was significantly reduced by TTX, suggesting that a part of the contraction was produced by activation of NANC excitatory nerves. Thus, the esophageal smooth muscle of the frog demonstrates myogenic activity, and is innervated by both excitatory and inhibitory NANC nerves.