Calcium Sensitization Mechanisms in Gastrointestinal Smooth Muscles

An increase in intracellular Ca2+ is the primary trigger of contraction of gastrointestinal (GI) smooth muscles. However, increasing the Ca2+ sensitivity of the myofilaments by elevating myosin light chain phosphorylation also plays an essential role. Inhibiting myosin light chain phosphatase activity with protein kinase C-potentiated phosphatase inhibitor protein-17 kDa (CPI-17) and myosin phosphatase targeting subunit 1 (MYPT1) phosphorylation is considered to be the primary mechanism underlying myofilament Ca2+ sensitization. The relative importance of Ca2+ sensitization mechanisms to the diverse patterns of GI motility is likely related to the varied functional roles of GI smooth muscles. Increases in CPI-17 and MYPT1 phosphorylation in response to agonist stimulation regulate myosin light chain phosphatase activity in phasic, tonic, and sphincteric GI smooth muscles. Recent evidence suggests that MYPT1 phosphorylation may also contribute to force generation by reorganization of the actin cytoskeleton. The mechanisms responsible for maintaining constitutive CPI-17 and MYPT1 phosphorylation in GI smooth muscles are still largely unknown. The characteristics of the cell-types comprising the neuroeffector junction lead to fundamental differences between the effects of exogenous agonists and endogenous neurotransmitters on Ca2+ sensitization mechanisms. The contribution of various cell-types within the tunica muscularis to the motor responses of GI organs to neurotransmission must be considered when determining the mechanisms by which Ca2+ sensitization pathways are activated. The signaling pathways regulating Ca2+ sensitization may provide novel therapeutic strategies for controlling GI motility. This article will provide an overview of the current understanding of the biochemical basis for the regulation of Ca2+ sensitization, while also discussing the functional importance to different smooth muscles of the GI tract.

The Study on Content of Myosin Light Chain Phosphatase of SHR' Different Organs / 医学研究杂志

Objective To investigate the relationship between MLCP and hypertension pathomechanism of SHR by comparing 130 kD、38 kD、21 kD subunits in aorta,heart,kidney and brain of spontaneously hypertensive rat(SHR) and Wistar Kyoto rat(WKY).Methods The aorta,heart,kidney and brain were obtained from 10 SHRs and 10 WKY rats,and each tissue was freshly removed and weighed and rapidly frozen in liquid nitrogen,homogenized with buffer solution,total protein concentration was rectified according to the methods of Bradford,and SDS-PAGE、Western blots and chemo-luminescence were carried out to determine the content of three subunits,the results were estimated by ABS.t-Test and ANOVA were used to analyzed data.Results The contents of 130kDa,38kDa,21kDa subunits of SHR among the different organs were markedly different,the highest contents of 130kDa was located in the aorta;but the kidney had the highest contents of 38kDa subunit and 21kDa subunit was the highest in the aorta too.Conclusion The difference among the contents of 130kDa subunit、38kDa subunit and 21kDa subunit of SHR and WKY in the different organs implied that abnormity of MLCP' structure and function was associated with hypertension pathomechanism of SHR.