Gastric contractions show two specific patterns in many species, migrating motor contractions (MMC) and postprandial contractions (PPCs), that occur in the fasted and fed states, respectively. In this study, we examined the role of somatostatin (SST) in gastric motility both in vivo and in vitro using the Asian house shrew (Suncus murinus). We performed in vivo recordings of gastric motility and in vitro organ bath experiments using S. murinus, which was recently established as a small laboratory animal for use in tests of gastrointestinal motility. SST (1.65 µg kg⁻¹ min⁻¹) was intravenously administered during phase II of MMC and PPCs. Next, the effect of SST on motilin-induced gastric contractions at phase I of MMC was measured. Cyclosomatostatin (CSST), an SST receptor antagonist, was administered at the peak of phase III of MMC. In addition, the effect of SST (10⁻¹¹–10⁻⁹ M) on motilin-induced gastric contractions was evaluated using an organ bath experiment in vitro. In conscious, free-moving S. murinus, the administration of SST decreased the occurrence of the spontaneous phase II of MMC and PPCs. Pretreatment with SST and octreotide suppressed the induction of motilin-induced gastric contractions both in vivo and in vitro. Administration of CSST before the peak of spontaneous phase III contractions had no effect on gastric contractions. Endogenous SST is not involved in the regulation of gastric MMC and PPCs, but exogenous SST suppresses spontaneous gastric contractions. Thus, SST would be good for treating abnormal gastrointestinal motility disorders.

Oropharyngeal dysphagia (OD) is a common symptom in the older people, and may cause fatal complications such as aspiration pneumonia. However, there is no established treatment for OD. The relationship between the transient receptor potential vanilloid 1 (TRPV1) and substance P released by activated TRPV1 was recently demonstrated. Further, there are several reports showing that capsaicin, a specific agonist of TRPV1, can improve OD. Currently, the evaluation of swallowing is mainly performed by videofluoroscopic examination. However, there are no reports on the clinical application of ultrasonography using tissue Doppler imaging. In this review, we describe the pathophysiology and treatments for OD, introduce our novel US method to evaluate cervical esophageal motility, and then outline our clinical study examining the effects of capsaicin, a specific TRPV1 agonist, in older patients with OD.

Blebbistatin, a potent inhibitor of myosin II, is known to suppress smooth muscle contraction without affecting myosin light chain phosphorylation level. In order to clarify the regulatory mechanisms of blebbistatin on phasic and tonic smooth muscles in detail, we examined the effects of blebbistatin on relaxation process by Ca²⁺ removal after Ca²⁺-induced contraction of β-escin skinned (cell membrane permeabilized) trachea and taenia cecum preparations from guinea pigs. Blebbistatin significantly suppressed the force during relaxation both in skinned trachea and taenia cecum. The data fitting analysis of the relaxation processes indicates that blebbistatin accelerates slow (latch-like) bridge dissociation.

The c-Kit receptor tyrosine kinase regulates the development and differentiation of several progenitor cells. In the gastrointestinal (GI) tract, the c-Kit regulates the development of the interstitial cells of Cajal (ICC) that are responsible for motility regulation of the GI musculature. W-sash (W^sh) is an inversion mutation upstream of the c-kit promoter region that affects a key regulatory element, resulting in cell-type-specific altered gene expression, leading to a decrease in the number of mast cells, melanocytes, and ICC. We extensively examined the GI tract of W^sh/W^sh mice using immunohistochemistry and electron microscopy. Although the musculature of the W^sh/W^sh mice did not show any c-Kit immunoreactivity, we detected intensive immunoreactivity for transmembrane member 16A (TMEM16A, anoctamin-1), another ICC marker. TMEM16A immunopositive cells were observed as ICC-MY in the gastric corpus-antrum and the large intestine, ICC-DMP in the small intestine, and ICC-SM in the colon. Electron microscopic analysis revealed these cells as ICC from their ultrastructural features, such as numerous mitochondria and caveolae, and their close contact with nerve terminals. In the developmental period, we examined 14.5 and 18.5 day embryos but did not observe c-Kit immunoreactivity in the W^sh/W^sh small intestine. From this study, ICC subtypes developed and maturated structurally without c-Kit expression. W^sh/W^sh mice are a new model to investigate the effects of c-Kit and unknown signaling on ICC development and function.

Spontaneous rhythmic constrictions known as vasomotion are developed in several microvascular beds in vivo. Vasomotion in arterioles is considered to facilitate blood flow, while venular vasomotion would facilitate tissue metabolite drainage. Mechanisms underlying vasomotion periodically generate synchronous Ca²⁺ transients in vascular smooth muscle cells (VSMCs). In visceral organs, mural cells (pericytes and VSMCs) in arterioles, capillaries and venules exhibit synchronous spontaneous Ca²⁺ transients. Since sympathetic regulation is rather limited in the intra-organ microvessels, spontaneous activity of mural cells may play an essential role in maintaining tissue perfusion. Synchronous spontaneous Ca²⁺ transients in precapillary arterioles (PCAs)/capillaries appear to propagate to upstream arterioles to drive their vasomotion, while venules develop their own synchronous Ca²⁺ transients and associated vasomotion. Spontaneous Ca²⁺ transients of mural cells primarily arise from IP₃ and/or ryanodine receptor-mediated Ca²⁺ release from sarcoendoplasmic reticulum (SR/ER) Ca²⁺ stores. The resultant opening of Ca²⁺-activated Cl^- channels (CaCCs) causes a membrane depolarisation that triggers Ca²⁺ influx via T-type and/or L-type voltage-dependent Ca²⁺ channels (VDCCs). Mural cells are electrically coupled with each other via gap junctions, and thus allow the sequential spread of CaCC or VDCC-dependent depolarisations to develop the synchrony of Ca²⁺ transients within their network. Importantly, the synchrony of spontaneous Ca²⁺ transients also requires a certain range of the resting membrane potential that is maintained by the opening of K_v7 voltage-dependent K⁺ (K_v7) and inward rectifier K⁺ (K_ir) channels. Thus, a depolarised membrane would evoke asynchronous, ‘premature’ spontaneous Ca²⁺ transients, while a hyperpolarised membrane prevents any spontaneous activity.