Regulation of Smooth Muscle Contractility

Asthma is a complex respiratory disorder that involves mast cell degranulation, mucous secretions, and smooth muscle hypertrophy and hyperresponsiveness. Smooth muscle hyperresponsiveness has suggested some defect in the regulation of smooth muscle contractility. Therefore, a number of studies concerning asthma have centered on whether alterations in the regulation of smooth muscle contraction (Figure 4) are responsible for hyperactivity in asthmatic airway smooth muscle. 

Hollenberg, M.D. 1994. Tyrosine kinase pathways and the regulation of smooth muscle contractility. Trends Pharmacol Sci 15 108-114. 

Nishimura, J. and van Breemen, C. (1989). Direct regulation of smooth muscle contractile elements by second messenger. Biochem. Biophys. Res. Comm. 163, 929-935. 

Nishimura J, van Breemen C (1989) Direct regulation of smooth muscle contractile elements by second messengers. Biochem Biophys Res Commun 163 929-935 Nishimura J, Kolber M, van Breemen C (1988) Norepinephrine and GTP-y-S increase myofilament Ca " sensitivity in a-toxin permeabilized arterial smooth muscle. Biochem Biophys Res Commun 157 677-683 Nishiye E, Somlyo AV, Torok K, Somlyo AP (1993) The effects of MgADP on crossbridge kinetics a laser flash photolysis study of guinea-pig smooth muscle. J Physiol (Lond) 460 247-271... 

Nobe K, Sutliff RL, Kranias EG, Paul RJ 2001 Phospholamban regulation of bladder contractility evidence from gene-altered mouse models. J Physiol 535 867-878 Paul RJ 1998 The role of phospholamban and SERCA3 in regulation of smooth muscle-endothelial cell signalling mechanisms evidence from gene-ablated mice. Acta Physiol Scand 164 589—597... 

Our understanding of smooth muscle contractility and its regulation has frequently lagged behind that of skeletal and cardiac muscle. Although this situation is improving, fundamental questions regarding the mechanism of smooth muscle function remain unresolved. In this chapter, some have been highlighted and include ... 

Somatostatin acts on various organs, tissues and cells as neurotransmitter, paracrine/autocrine and endocrine regulator on cell secretion, smooth muscle contractility, nutrient absorption, cell growth and neurotransmission [1]. Some of its mainly inhibitory effects are listed in Table 1. Somatostatin mediates its function via a family of heptahelical G-protein-coupled receptors termed... 

Major effector proteins for G-pro-tein-coupled receptors include adenylate cyclase (ATP intracellular messenger cAMP), phospholipase C (phos-phatidylinositol intracellular messengers inositol trisphosphate and di-acylglycerol), as well as ion channel proteins. Numerous cell functions are regulated by cellular cAMP concentration, because cAMP enhances activity of protein kinase A, which catalyzes the transfer of phosphate groups onto functional proteins. Elevation of cAMP levels inter alia leads to relaxation of smooth muscle tonus and enhanced contractility of cardiac muscle, as well as increased glycogenolysis and lipolysis (p. 

Acting as an intracellular second messenger, cAMP mediates such hormonal responses as the mobilization of stored energy (the breakdown of carbohydrates in liver or triglycerides in fat cells stimulated by B-adrenomimetic catecholamines), conservation of water by the kidney (mediated by vasopressin), Ca2+ homeostasis (regulated by parathyroid hormone), and increased rate and contractile force of heart muscle ( -adrenomimetic catecholamines). It also regulates the production of adrenal and sex steroids (in response to corticotropin or follicle-stimulating hormone), relaxation of smooth muscle, and many other endocrine and neural processes. 

S ATP + myosin hght chain <1-12> (<1, 2, 8> event in initiation of smooth-muscle contraction [5] <8> involved in regulation of actin-myosin contractile activity in adrenal medulla [7] <8> obhgatory step in development of active tension in smooth muscle [13] <5> involved in myosin phosphorylation and enzyme secretion [16] <2, 3, 5, 6, 8, 10, 11> involved in muscle contractility and motility of non-muscle cells [33] <2> inhibition of actin-myosin ineraction [36,37]) (Reversibihty 1-12 [1-33]) [1-33]... 

Although much of the focus has been on the DPC of striated muscle, it is likely that desmin attachments to dense plaques of smooth muscle play critical roles in regulating the transmission of contractile forces in this tissue as well. This is particularly relevant in light of the observed defects in smooth muscle of desmin-deficient mice, in which active force per cross-sectional area was reduced to 40% of controls of smooth muscle tissue (Sjuve et al, 1998). IFAP candidates for serving this linking function are plectin and other components of the actin-rich cortex, including calponin (which also plays a role in the cytoplasm of smooth muscle cell dense bodies see below), and the spectrin/ankyrin complex. 

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